In seasonal mammals the duration of nocturnal melatonin secretion accurately reflects the environmental photoperiod. The endocrine rhythm is decoded by a specialised portion of the pituitary gland (the pars tuberalis, PT) which then relays this information to the pars distalis and hypothalamus, precipitating huge annual changes in physiology and behaviour. However how the PT decodes the melatonin signal is currently unknown. Melatonin influences gene transcription in the ovine PT at its onset and offset, and the phase relationship of these two groups is believed to form the underlying mechanism by which the PT integrates seasonal time. The transcripts induced at melatonin offset are understood to be under the control of a seasonally gated cAMP mechanism. Conversely processes involved in melatonin-mediated gene induction are currently not understood.The work in this thesis ultimately aims to reveal how the seasonal melatonin signal is decoded by the PT. To this end melatonin-mediated gene induction has been characterised through RNAseq, the highly displaced cohorts submitted to bioinformatic promoter analysis and the paradigm tested though in vitro modelling techniques.In this study a 1.5 h infusion with melatonin acutely regulated 219 transcripts in the ovine PT (115 induced, 104 repressed, >1.5 fold change), confirming previous association of several genes (including Cry1, MT1, Gadd45g, Nampt and Npas4) to rapid melatonin control. Gross promoter analysis of these groups indicated that the induced gene cohort was significantly enriched for GC content and CpG islands suggesting the involvement of epigenetic mechanisms of transcriptional control. Further bioinformatic analysis specifically implicated the importance of transcription factors ZFP161 and PAX5 in melatonin-mediated gene induction in the PT. Several immortalised cell lines were screened for the presence of a functional melatonin receptor. Two strains (MCF7 oMT1 and NES2Y) exhibited significant attenuation of forskolin-mediated cAMP accumulation when co-treated with melatonin, a hallmark of melatonin Gαi-coupled protein receptor signalling. These lines were subsequently evaluated as models of melatonin-mediated gene induction of the sheep PT through ovine promoter reporter assays of Cry1, Nampt, NeuroD1 and Npas4. However, treatment with melatonin failed to evoke a reporter response suggesting that the cell line models were inadequately equipped to reflect PT biology. Subsequently a protocol was established to culture ovine PT explants culture which faithfully recapitulated melatonin mediated transcriptional dynamics in vitro, providing a possible tool for the future investigation of the PT. Lastly, previous work has shown the transcriptional profile of Npas4 to peak highly and transiently, pre-empting the expression of other melatonin-induced genes. Using a COS7 cell line model, heterologously-expressed NPAS4 was shown to form functional heterodimeric partnerships with ARNT and ARNTL and transactivate both Cry1 and Nampt promoter reporters through novel binding sites. Collectively these data indicated NPAS4 to act as an immediate activator of melatonin regulated circuits

No description available.

Yes / Animals have evolved diverse seasonal variations in physiology and reproduction to accommodate yearly changes in environmental and climatic conditions. These changes in physiology are initiated by changes in photoperiod (daylength) and are mediated through melatonin, which relays photoperiodic information to the pars tuberalis of the pituitary gland. Melatonin drives thyroid‐stimulating hormone transcription and synthesis in the pars tuberalis, which, in turn, regulates thyroid hormone and retinoic acid synthesis in the tanycytes lining the third ventricle of the hypothalamus. Seasonal variation in central thyroid hormone signalling is conserved among photoperiodic animals. Despite this, different species adopt divergent phenotypes to cope with the same seasonal changes. A common response amongst different species is increased hypothalamic cell proliferation/neurogenesis in short photoperiod. That cell proliferation/neurogenesis may be important for seasonal timing is based on (i) the neurogenic potential of tanycytes; (ii) the fact that they are the locus of striking seasonal morphological changes; and (iii) the similarities to mechanisms involved in de novo neurogenesis of energy balance neurones. We propose that a decrease in hypothalamic thyroid hormone and retinoic acid signalling initiates localised neurodegeneration and apoptosis, which leads to a reduction in appetite and body weight. Neurodegeneration induces compensatory cell proliferation from the neurogenic niche in tanycytes and new cells are born under short photoperiod. Because these cells have the potential to differentiate into a number of different neuronal phenotypes, this could provide a mechanistic basis to explain the seasonal regulation of energy balance, as well as reproduction. This cycle can be achieved without changes in thyroid hormone/retinoic acid and explains recent data obtained from seasonal animals held in natural conditions. However, thyroid/retinoic acid signalling is required to synchronise the cycles of apoptosis, proliferation and differentiation. Thus, hypothalamic neurogenesis provides a framework to explain diverse photoperiodic responses. / MRC. Grant Number: MR/P012205/1 - Scottish Government - BBSRC. Grant Number: BB/K001043/1 - Physiological Society

Ce travail de neurobiologie intégrative porte sur l’étude des contrôles exercés par les récepteurs 5-HT2C au niveau du réseau des ganglions de la base, un groupe de structures sous-corticales impliquées dans le contrôle du comportement moteur. Les récepteurs 5-HT2C exercent trois modalités de contrôle sur les cellules des ganglions de la base comprenant les contrôles phasique, tonique et constitutif, ce dernier contrôle étant indépendant de la présence de la sérotonine (5-HT), le ligand endogène. A l’aide d’outils pharmacologiques appropriés (agoniste, antagoniste et agoniste inverse), nous avons étudié chez le rat les différents contrôles des récepteurs 5-HT2C sur un comportement moteur, les mouvements orofaciaux. Nous avons aussi étudié ces contrôles dans les ganglions de la base en mesurant l’expression du marqueur neuronal de changement d’activité cellulaire, le proto-oncogène c-Fos, et en utilisant des enregistrements extracellulaires unitaires de la fréquence basale ou évoquée par des stimulations corticales des structures de sortie du réseau, le noyau entopédonculaire (NEP) ou la substance noire pars reticulata (SNr). Mes données montrent que la stimulation du récepteur 5-HT2C ou le blocage de son activité constitutive entrainent une augmentation des mouvements orofaciaux anormaux. Les données anatomiques révèlent que les différents contrôles 5-HT2C s’expriment au niveau des structures d’entrées des ganglions de la base, le striatum et le noyau sous-thalamique (NST), avec une expression préférentielle de l’activité constitutive au niveau du striatum et du noyau accumbens (NAc). Le contrôle phasique et l’activité constitutive étendent leur influence vers les structures de sortie des ganglions de la base ce qui pourrait être associé à l’émergence des mouvements orofaciaux anormaux. Les contrôles 5-HT2C sont influencés par le niveau d’activité du réseau et notamment le niveau de transmission dopaminergique (DA). En effet, une lésion des neurones DA potentialise les réponses comportementales et électrophysiologiques induites par un agoniste 5-HT2C au niveau du NEP. La stimulation des récepteurs D2 entraîne des dyskinésies orofaciales et une augmentation des réponses électrophysiologiques de la voie cortico-sous-thalamo-nigrale et ces effets sont supprimés par des antagonistes 5-HT2C. Ce travail apporte des éléments concernant la distribution et la nature de divers contrôles exercés par les récepteurs 5-HT2C au sein des ganglions de la base. Il ouvre des perspectives thérapeutiques sur l’utilisation des antagonistes 5-HT2C dans la schizophrénie ou la maladie de Parkinson. Pour autant, ces contrôles sont complexes et une meilleure connaissance de leur rôle dans ces régions permettrait de mieux appréhender des thérapies éventuelles avec des agents 5-HT et/ou 5-HT2C. / This work of integrative neurobiology focuses on the study of the controls exerted by the 5-HT2C receptors in the basal ganglia, a group of subcortical structures involved in the control of motor behavior. 5-HT2C receptors exert three modalities of control over cells of the basal ganglia, including a phasic, tonic and a constitutive control, the latter one being independent of the presence of serotonin (5-HT), the endogenous ligand. Using appropriate pharmacological tools (agonist, antagonist and inverse agonist), we have studied in rats the different controls of 5-HT2C receptors on one motor behavior, the purposeless orofacial movements. We also have studied these controls in the basal ganglia by measuring the expression of the proto-oncogene c-Fos, a marker of change of neuronal activity by determining the firing rate, basal or evoked by cortical stimulations, of neurons located in the output structures, the entopeduncular nucleus (EPN) or the substantia nigra pars reticulata (SNr), using single unit extracellular recordings. My data showed that stimulation or the blockade of the constitutive activity of 5-HT2C receptor induced an increase in abnormal orofacial movements. Anatomical data indicated that the different 5-HT2C controls are expressed in the input structures of the basal ganglia, the striatum and the subthalamic nucleus (STN), with a preferential influence of the constitutive activity in the striatum and nucleus accumbens (NAc). In addition, the phasic control and the constitutive activity extended their control to the output structures of the basal ganglia which could be associated with the emergence of orofacial movements. 5-HT2C controls are influenced by the network activity, in particular the level of dopaminergic (DA) transmission. Indeed, a lesion of DA neurons potentiated behavioral and electrophysiological responses induced by a 5-HT2C agonist by acting in the EPN. The stimulation of D2 receptors induced oral dyskinesia and an increase in electrophysiological responses of the cortico-subthalamo-nigral pathway, and these effects were suppressed by selective 5-HT2C antagonists. This work brings up elements regarding the distribution and the nature of the diverse controls exerted by 5-HT2C receptors in the basal ganglia. It opens therapeutic perspectives for the use of 5-HT2C antagonists in the treatment of schizophrenia and Parkinson's disease. Nevertheless, these controls are complex and a better understanding of these controls in these regions would permit to apprehend possible treatments using 5-HT and/or 5-HT2C agents.

Submitted by Automa??o e Estat?stica (sst@bczm.ufrn.br) on 2016-04-08T23:56:19Z No. of bitstreams: 1 JoseRodolfoLopesDePaivaCavalcanti_TESE.pdf: 2156602 bytes, checksum: 000c3eafedc8a66a1a55425b0168fd4a (MD5) / Approved for entry into archive by Arlan Eloi Leite Silva (eloihistoriador@yahoo.com.br) on 2016-04-11T23:46:45Z (GMT) No. of bitstreams: 1 JoseRodolfoLopesDePaivaCavalcanti_TESE.pdf: 2156602 bytes, checksum: 000c3eafedc8a66a1a55425b0168fd4a (MD5) / Made available in DSpace on 2016-04-11T23:46:45Z (GMT). No. of bitstreams: 1 JoseRodolfoLopesDePaivaCavalcanti_TESE.pdf: 2156602 bytes, checksum: 000c3eafedc8a66a1a55425b0168fd4a (MD5) Previous issue date: 2015-04-30 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior - CAPES / Conselho Nacional de Desenvolvimento Cient?fico e Tecnol?gico - CNPq / Sabe-se que o grupo das catecolaminas ? integrado pela dopamina, noradrenalina e adrenalina e que a s?ntese dessas subst?ncias se d? de modo sequencial, sendo a enzima tirosina-hidroxilase reguladora da fase inicial deste processo. Neste sentido, a 3- hidroxitiramina/dopamina ? precursora da s?ntese de noradrenalina e adrenalina e ainda possui a capacidade de atuar como neurotransmissor na por??o central do sistema nervoso. Os tr?s principais n?cleos dopamin?rgicos, chamados zona retrorubral (grupo A8), subst?ncia negra pars compacta (grupo A9) e ?rea tegmentar ventral (grupo A10), est?o dispostos na por??o die-mesencef?lica e est?o envolvidos em tr?s vias, a mesostriatal, mesol?mbica e mesocortical. Estas vias est?o relacionadas diretamente com diversas manifesta??es comportamentais como controle da motricidade, sinaliza??o de recompensa na aprendizagem comportamental, motiva??o e nas manifesta??es patol?gicas da Doen?a de Parkinson e esquizofrenia. Considerando-se a relev?ncia desses, o objetivo do trabalho foi caracterizar morfologicamente os n?cleos dopamin?rgicos (A8, A9 e A10) do sagui (Callithrix jacchus) mediante estudo citoarquitet?nico e imunoistoqu?mico contra tirosina-hidroxilase. O sag?i ? um primata neotropical, cujas caracter?sticas morfofuncionais repercutem na adequabilidade de uso deste animal em pesquisas de ordem biom?dica. Sec??es coronais dos enc?falos de seis animais foram submetidas ? colora??o pelo m?todo de Nissl e immunoistoqu?mica para tirosinsa-hidroxilase. Com base na morfologia dos neur?nios, foi poss?vel subdividir o grupo A10 em sete regi?es: n?cleo interfascicular, linear rostral e linear caudal, situados na linha m?dia; paranigral e o parainterfascicular, situados na zona intermedi?ria; a por??o rostral da ?rea tegmentar ventral e o n?cleo parabraquial pigmentado, situados na por??o dorsolateral do tegmento mesencef?lico. O grupo A9 foi subdividido em quatro regi?es: subst?ncia negra camadas dorsal e ventral; subst?ncia negra conjuntos lateral e medial. Por ?ltimo, n?o foram indentificadas subdivis?es no grupo A8. Conclu?-se que A8, A9 e A10 s?o filogeneticamente conservados entre as esp?cies, por?m percebe-se a necessidade de se ampliar os estudos acerca das organiza??es subnucleares, seja investigando a sua ocorr?ncia em outras esp?cies de primatas, seja investigando a sua relev?ncia funcional. / It is known that the catecholamine group is constituted by dopamine, noradrenaline and adrenaline, in which the synthesis is regulated by an enzyme named tyrosine hydroxylase. Thus, 3-hydroxytyramine/dopamine (DA) is a precursor of the noradrenaline and adrenaline synthesis and acts as a neurotransmitter in the central nervous system. The three main nuclei, named the retrorubral field (A8 group), the substantia nigra pars compacta (A9 group) and the ventral tegmental area (A10 group), are arranged in the die-mesencephalic portion and are involved in three complexes circuitries - the mesostriatal, mesolimbic and mesocortical pathways. These pathways are related to behavioral manifestations, motricity, learning, reward and pathologies such as Parkinson?s Disease and Schizophrenia. Thus, the aim of this study was to perform de morphological analysis of the A8, A9 and A10 nuclei of the common marmoset (Callithrix jacchus). The marmoset is a neotropical primate, whose morphological and functional characteristics supports the suitability of use of this animal in biomedical research. Coronal sections of the marmoset brain were submitted to cytoarchitectonic characterization and TH-immunohistochemistry. Based on the morphology of the neurons, it was possible to subdivide the A10 group in seven regions: interfascicular nucleus, raphe rostral linear nucleus and raphe caudal linear nucleus, in the middle line; paranigral and parainterfascicular nucleus, in the middle zone; rostral portion of the ventral tegmental area nucleus and parabrachial pigmented nucleus, located in the dorsolateral portion of the mesencephalic tegmentum. A9 group was divided into four regions: substantia nigra compacta dorsal and ventral tiers; substantia nigra compacta lateral and medial clusters. No subdivisions were founded into A8 group. These results revealed that A8, A9 and A10 are phylogenetically conserved between species, but it?s necessary to expand the studies about this compartmentalization, investigating its occurrence in other primate species or investigating its functional relevance.

In der Humanmedizin wird zur Beurteilung der Magenschleimhautproben das aktualisierte Sydney-System nach STOLTE (1997) angewendet. Das Ziel war es herauszufinden, ob das histologische Grading System auch in der Veterinärmedizin, für die Beurteilung von Pferdemagenschleimhautpräparaten, genutzt werden kann und ob daraus neue Erkenntnisse erwachsen. Von 60 Pferden wurden direkt post mortem Schleimhautproben aus der Pars glandularis (Drüsenschleimhaut), im Bereich der großen Kurvatur und dem Pylorus, entnommen. Die Patienten wurden in 4 Gruppen, 10 operierte (Kolik)pferde, 36 Pferde mit Kolik und infauster Prognose, 6 Pferde mit hochgradigen Magenulzera und 8 Pferde, die nicht auf Grund einer Kolik euthanasiert wurden, eingeteilt. Die makroskopische Beurteilung der 60 Pferdemägen erfolgte nach MURRAY et al. (1989) und MACALLISTER et al. (1995). Die histopathologische Beurteilung erfolgt in der Humanmedizin anhand der Helicobacter-like-Organismen Dichte, dem Grad der chronischen Entzündung, der Aktivität der Gastritis, der Atrophie und der intestinalen Metaplasie. Nach diesen Beurteilungsvariablen wurden die 120 Proben aus den 60 Pferdemägen beurteilt. Die ätiologischen Diagnosen sind in der Humanmedizin das Ergebnis jahrzehntelanger Forschung. Beim Pferd liegen dagegen zur Ätiologie der Gastritis noch keine gesicherten Erkenntnisse vor. Beim Pferd gibt es bestimmte Gastritisformen, die denen des Menschen ähnlich sind. Doch können die morphologischen Befunde in der Veterinärmedizin, nach den jetzigen Erkenntnissen, keinen Ätiologien zugeordnet werden. Die ätiologischen Diagnosen in dieser veterinärmedizinischen Studie beruhen auf der Diagnostik am Menschen und wurden noch nicht auf ihre Richtigkeit beim Pferd überprüft. Von den 60 untersuchten Pferdemägen wiesen 31 makroskopisch Läsionen in der Magenschleimhaut auf. 20 Pferde mit Veränderungen hatten diese in der Pars glandularis. Bei 44 der Pferde bestätigt der histologische Befund, nach dem aktualisierten Sydney- System, das makroskopische Grading. 13 der Pferde hatten nach dem aktualisierten Sydney-System histologisch einen pathologischen Befund, obwohl makroskopisch die Schleimhaut keine Auffälligkeiten aufwies. Bei nur 3 von den 60 Pferden konnte der histologische den makroskopischen Befund nicht bestätigen. Ätiologisch wurde, nach humanmedizinischen Beurteilungskriterien, bei 18 Pferden im Bereich der großen Kurvatur der Pars glandularis und, oder im Bereich des Pylorus eine C-Gastritis (chemische Gastritis), bei 11 Pferden eine like B-Gastritis (bakterielle Gastritis ohne den Nachweis von Helicobacter-like-Organismen), 3 Pferden eine B-Gastritis (bakterielle Gastritis mit dem Nachweis von Helicobacter-like-Organismen) und bei 9 Pferden eine Sonderform der Gastritis diagnostiziert. 6 Pferde bekamen die Diagnose: zur Zeit nicht klassifizierbar und 7 Pferde die deskriptive Diagnose erosive oder ulzerative Gastritis gestellt. 24 Pferde hatten keinen pathologischen Befund in einem der oben genannten Bereiche der Schleimhaut. Die histopathologischen Befunde der Pferde mit einer like-B-Gastritis oder einer B-Gastritis entsprachen nach humanmedizinischen Gesichtspunkten dem Bild einer Helicobacter-pylori-Gastritis beim Menschen. Bandartige Anordnung der Lymphozyten in der Lamina propria mucosae und neutrophile Granulozyten in Verbindung mit einer Atrophie des Drüsenkörpers, intestinaler Metaplasie und Erosionen. Bei drei Pferden konnte in der Warthin–Starry-Färbung und in der IHC-Reaktion Helicobacter-like-Organismen nachgewiesen werden. Die Pylorusschleimhaut war doppelt so häufig, im Vergleich zur Drüsenschleimhaut der großen Kurvatur, von einer like-B-Gastritis oder B-Gastritis betroffen. Die histologische Auswertung von Magenschleimhautbioptaten, in dieser Studie nach dem aktualisierten Sydney-System aus der Humanmedizin, komplettiert die makroskopische (endoskopische) Diagnostik. Nach den Ergebnissen der vorliegenden Studie gehört in der Pferdemedizin zu jeder Gastroskopie die Bioptatentnahme. Das aktualisierte Sydney-System kann in Zukunft in der Veterinärmedizin als Arbeitsgrundlage für die weitere wissenschaftliche Forschung genutzt werden.:Inhaltsverzeichnis Seite 1 Einleitung und Problemstellung 1 2 Literaturübersicht 2 2.1 Die makroskopische Anatomie des Pferdemagens 2 2.2 Histologie des Pferdemagens 4 2.2.1 Bau der Magenwand 4 2.2.2 Pars glandularis 4 2.2.2.1 Gemischte Kardia- und Pylorusdrüsenzone 5 2.2.2.2 Fundus- oder Eigendrüsenzone der großen Kurvatur 5 2.2.2.3 Pylorusdrüsenzone 5 2.2.3 Pars nonglandularis 6 2.2.4 Magendrüsen 6 2.2.5 Zelltypen der Magendrüsen 6 2.2.5.1 Schleimproduzierende Zellen 6 2.2.5.2 Belegzellen (Parietalzellen) 7 2.2.5.3 Hauptzellen 8 2.2.5.4 Weitere Zellen der Drüsenschleimhaut 9 2.3 Magenschleimhautbarriere und weitere Schutzmechanismen der Pars glandularis 10 2.3.1 Bicarbonat-Schleimsekret 10 2.3.2 Epitheliale Regeneration 10 2.3.3 Schleimhautdurchblutung 11 2.3.4 Prostaglandin E2 (PGE2) 11 2.3.5 Speichelproduktion und Duodenalreflux 11 2.3.6 Protein und Kalzium 12 2.3.7 Epidermaler Wachstumsfaktor (Epidermal Growth Factor, EGF) 12 2.4 Schutzmechanismen der Pars nonglandularis 13 2.5 Pathologische Veränderungen in der Schleimhaut des Pferdemagens 13 2.5.1 Makroskopische und mikroskopische Schleimhautveränderungen in der Pars glandularis und Pars nonglandularis 13 2.5.1.1 Erosionen und Ulzera (EGUS: equine gastric ulcer syndrome) 13 2.5.1.2 Desquamation und Verhornungsstörungen 14 2.5.1.3 Gastritis (Mensch und Pferd) 15 2.5.1.4 Helicobacter-like-Gastritis 16 2.5.1.4.1 Geschichte der Helicobacter-Forschung 16 2.5.1.4.2 Gastrale Helicobacterspezies 17 2.5.1.4.2.1 Helicobacter spp. beim Tier 17 2.5.1.4.2.2 Helicobacter pylori (H. pylori) 20 2.5.1.4.2.3 Infektion mit Helicobacter pylori 21 2.6 Methoden zum Nachweis von Helicobacter spp. 22 2.6.1 Histologischer Nachweis von Helicobacter pylori 22 2.6.2 Immunhistochemische Techniken (IHC) 22 2.6.3 Molekularbiologische Testmethoden 23 2.6.4 Mikrobiologischer Nachweis (Bakterienkultur) 23 2.6.5 Urease-Schnelltest 24 2.6.6 13C-Atemtest 24 2.6.7 15N-Urintest und 13C-Serumtest 24 2.6.8 Stuhl-Test 25 2.6.9 Serologie 25 2.7 Makroskopische veterinärmedizinische Klassifizierung der Magenschleimhautläsionen nach MURRAY et al. (1989) und MACALLISTER et al. (1995) 25 2.7.1 Bewertungssystem nach MURRAY et al. (1989): Grad 1-4 25 2.7.2 Bewertungssystem nach MACALLISTER et al. (1995), modifiziert nach LUNDBERG (1995): Werte I-IV 26 2.8 Histologische Gastritis-Klassifizierung nach dem aktualisierten Sydney-System aus der Humanmedizin nach STOLTE et al. 1997 26 2.8.1 Entstehung des Sydney-Systems nach STOLTE et al. 1990 (STOLTE 1997) 26 2.8.2 Das aktualisierte Sydney-System nach STOLTE et al. 1997 (STOLTE 1997) 27 2.8.2.1 Klassifikation 27 2.8.2.2 Graduierung der morphologischen Variablen im histologischen Bild 28 2.8.2.3 Zu graduierende Variable 29 2.8.2.3.1 Helicobacter pylori – Dichte 29 2.8.2.3.2 Grad der chronischen Entzündung 29 2.8.2.3.3 Graduierung der Aktivität der Gastritis 30 2.8.2.3.4 Atrophie des Drüsenkörpers 31 2.8.2.3.5 Intestinale Metaplasie 31 2.8.2.4 Andere, nicht zu graduierende Variable 33 2.8.2.4.1 Oberflächenepithel, Schleimdepletion und Erosion 33 2.8.2.4.2 Lymphfollikel 33 2.8.2.4.3 Foveoläre Hyperplasie 34 2.8.2.5 Gastritiden 34 3 Eigene Untersuchungen 37 3.1 Material und Methodik 37 3.1.1 Patientenmaterial und Anamnese 37 3.1.2 Makroskopische Befundbeschreibung des eröffneten Magens 38 3.1.3 Gewebeproben 38 3.1.3.1 Probenentnahme und Bearbeitung 38 3.1.3.2 Histologische Bearbeitung der Proben 40 3.1.3.2.1 Hämatoxylin-Eosin-Färbung 41 3.1.3.2.2 Warthin-Starry-Färbung 41 3.1.3.2.3 Immunhistochemie (IHC) 41 3.1.4 Mikroskopische Befundbeschreibung nach dem aktualisierten Sydney-System nach STOLTE et al. 1997 42 3.1.5 Nachweis von Helicobacter-like-Organismen 43 3.1.5.1 Histologischer Nachweis 43 3.1.5.2 Molekularbiologische Testmethoden 43 3.1.6 Humanmedizinische Befundbeschreibung der ätiologischen Diagnosen nach dem aktualisierten Sydney-System (STOLTE et al. 1997) 45 3.2 Ergebnisse 46 3.2.1 Makroskopische Befundbeschreibung nach MURRAY et al. 1989 und nach MACALLISTER et al. 1995 46 3.2.2 Makroskopische Befundbeschreibung nach STOLTE et al. 1993 48 3.2.3 Mikroskopische humanmedizinische Beurteilung nach STOLTE et al. 1997 51 3.2.3.1 Histologische Beurteilung nach dem humanmedizinischen aktualisierten Sydney-System (STOLTE et al. 1997) 51 3.2.3.2 Histologische Beurteilung anhand der Hämatoxylin-Eosin- Färbung (HE) nach dem aktualisierten Sydney-System aus der Humanmedizin (STOLTE et al. 1997) 53 3.2.3.3 Histologische Beurteilung anhand der Warthin-Starry-Färbung und der immunhistochemische-Reaktion nach dem aktualisierten Sydney-System aus der Humanmedizin (STOLTE et al. 1997) 65 3.2.4 Histologische Befunde in der Drüsenschleimhaut bei Pferden mit Nachweis von Helicobacter-like-Organismen 66 3.2.5 Ätiologische Diagnosen nach dem aktualisierten Sydney-System aus der Humanmedizin (STOLTE et al. 1997) 76 3.2.6 Zusammenhang der makroskopischen und mikroskopischen Befunde 77 3.3 Ergebnisse der PCR 78 4 Diskussion 79 4.1 Methodik und Durchführung 79 4.2 Makroskopische Befunde 82 4.3 Mikroskopische Befunde 85 4.4 Helicobacter-like-Organismen, Häufigkeit, Lokalisation und Kolonisationsdichte 88 4.5 Einfluss der Besiedlung mit Helicobacter-like-Organismen auf die Gastritis und deren Behandlung 92 4.6 Ätiologische und deskriptive Diagnosen nach humanmedizinischen Kriterien 92 4.7 Veterinärmedizinische makroskopische Bewertungssysteme 95 4.8 Das humanmedizinische aktualisierte Sydney-System nach STOLTE et al. 1997 96 5 Zusammenfassung 99 6 Summary 101 7 Literaturverzeichnis 103 8 Anhänge 121 8.1 Anamneseprotokoll 121 8.1.1 Lebensalter, Geschlecht und Rasse der 60 Pferde 123 8.1.2 Klinische Diagnosen der 60 Pferde 125 8.1.3 Anamnese der 60 Pferde 128 8.2 Makroskopische Befundbeschreibung des eröffneten Magens nach STOLTE et al. (1993) 134 8.3 Makroskopische Klassifikation nach MURRAY et al. (1989) 136 8.4 Makroskopische Klassifikation nach MACALLISTER et al. (1995) modifiziert nach LUNDBERG (1995) 137 8.5 Makroskopische Beurteilung (Grading) 139 8.6 Graduierung nach dem aktualisierten Sydney-System STOLTE et al. (1997), im Vergleich dazu die makroskopische Beurteilung der Pars glandularis nach MACALLISTER et al. (1995) 141 8.7 Ätiologische oder deskriptive Diagnosen der 60 Pferde in der Pars glandularis der großen Kurvatur und dem Pylorus 146 9 Danksagungen 147 / Stolte’s updated Sydney system is used in the field of human medicine for grading the gastric mucosa (STOLTE 1997). The goal of this study was to determine whether this system could also be applied for histological parameter grading in veterinary medicine, in order to gain new insights into medications for treating equine gastric mucosa. Post mortem biopsies of mucosa were taken from 60 equines along the greater curve and pylorus of the pars glandularis. The test animals were divided into four groups: 10 post-colic surgery equines, 36 with colic and an infaust prognosis, six with chronic EGUS (equine gastric ulcer syndrome), and eight equines not euthanized for reasons other than colic. Macroscopic grading of the 60 equine stomachs was performed in accordance with MURRAY et al. (1989) and MACALLISTER et al. (1995). In human medicine, histological scoring is based on the following five parameters: density of Helicobacter-like organisms, grade of the chronic inflammation, level of gastric activity, atrophy, and intestinal metaplasia. A total of 120 biopsies taken from the 60 equines were graded according to these parameters. Etiologic diagnoses for humans are the outcome of decades of research, but the etiology of equine gastritis lacks an equivalent foundation. Equines exhibit forms of gastritis similar to those in humans, but their morphology cannot be classified into any specific etiology. In this study, the etiological diagnoses were based on human diagnostics, but their validity for equines has yet to be substantiated. Of the 60 equine stomachs examined, 31 showed lesions in the gastric mucosa, while 20 of those with changes had lesions in the pars glandularis. Histological findings of 44 equines confirmed the macroscopic grading according to the updated Sydney system. Thirteen equines exhibited pathological findings based on the updated Sydney system histology, although no abnormalities were discovered in the macroscopic examination. The histological diagnosis did not confirm the macroscopic grading for only three of the 60 subjects. The following etiological findings were reached in terms of human medicine: 18 equines with type C gastritis (chemical gastritis) along the greater curve of the pars glandularis and/or pylorus, 11 equines with type B-like gastritis (bacterial gastritis without evidence of H-like organisms), three equines with type B gastritis (bacterial gastritis with evidence of H-like organisms), and nine with a special form of gastritis. Six of the equines could not be classified, while seven showed erosive gastritis or ulceration. A total of 24 equines exhibited no pathological findings along any of the above-mentioned mucosae. The histopathological findings of the equines with either type B-like gastritis or type B gastritis corresponded with H pylori gastritis seen in humans, as ligamental lymphocytes in the lamina propria mucosae and neutrophilic granulocytes associated with atrophy of the glandular corpus, intestinal metaplasia, and erosion. Warthin-Starry staining and the IHC reaction confirmed H-like organisms in three of the equines. The frequency of type B-like gastritis or type B gastritis was observed to be twice as high in the pylorus mucosa as along the glandular mucosa of the greater curve. This study has demonstrated that histological analysis of gastric mucosa biopsies graded according to the updated Sydney system for human medicine significantly complements veterinary gastroscopy, which should therefore always include a biopsy. The updated Sydney system can thus serve as a platform for future scientific research in the field of veterinary medicine.:Inhaltsverzeichnis Seite 1 Einleitung und Problemstellung 1 2 Literaturübersicht 2 2.1 Die makroskopische Anatomie des Pferdemagens 2 2.2 Histologie des Pferdemagens 4 2.2.1 Bau der Magenwand 4 2.2.2 Pars glandularis 4 2.2.2.1 Gemischte Kardia- und Pylorusdrüsenzone 5 2.2.2.2 Fundus- oder Eigendrüsenzone der großen Kurvatur 5 2.2.2.3 Pylorusdrüsenzone 5 2.2.3 Pars nonglandularis 6 2.2.4 Magendrüsen 6 2.2.5 Zelltypen der Magendrüsen 6 2.2.5.1 Schleimproduzierende Zellen 6 2.2.5.2 Belegzellen (Parietalzellen) 7 2.2.5.3 Hauptzellen 8 2.2.5.4 Weitere Zellen der Drüsenschleimhaut 9 2.3 Magenschleimhautbarriere und weitere Schutzmechanismen der Pars glandularis 10 2.3.1 Bicarbonat-Schleimsekret 10 2.3.2 Epitheliale Regeneration 10 2.3.3 Schleimhautdurchblutung 11 2.3.4 Prostaglandin E2 (PGE2) 11 2.3.5 Speichelproduktion und Duodenalreflux 11 2.3.6 Protein und Kalzium 12 2.3.7 Epidermaler Wachstumsfaktor (Epidermal Growth Factor, EGF) 12 2.4 Schutzmechanismen der Pars nonglandularis 13 2.5 Pathologische Veränderungen in der Schleimhaut des Pferdemagens 13 2.5.1 Makroskopische und mikroskopische Schleimhautveränderungen in der Pars glandularis und Pars nonglandularis 13 2.5.1.1 Erosionen und Ulzera (EGUS: equine gastric ulcer syndrome) 13 2.5.1.2 Desquamation und Verhornungsstörungen 14 2.5.1.3 Gastritis (Mensch und Pferd) 15 2.5.1.4 Helicobacter-like-Gastritis 16 2.5.1.4.1 Geschichte der Helicobacter-Forschung 16 2.5.1.4.2 Gastrale Helicobacterspezies 17 2.5.1.4.2.1 Helicobacter spp. beim Tier 17 2.5.1.4.2.2 Helicobacter pylori (H. pylori) 20 2.5.1.4.2.3 Infektion mit Helicobacter pylori 21 2.6 Methoden zum Nachweis von Helicobacter spp. 22 2.6.1 Histologischer Nachweis von Helicobacter pylori 22 2.6.2 Immunhistochemische Techniken (IHC) 22 2.6.3 Molekularbiologische Testmethoden 23 2.6.4 Mikrobiologischer Nachweis (Bakterienkultur) 23 2.6.5 Urease-Schnelltest 24 2.6.6 13C-Atemtest 24 2.6.7 15N-Urintest und 13C-Serumtest 24 2.6.8 Stuhl-Test 25 2.6.9 Serologie 25 2.7 Makroskopische veterinärmedizinische Klassifizierung der Magenschleimhautläsionen nach MURRAY et al. (1989) und MACALLISTER et al. (1995) 25 2.7.1 Bewertungssystem nach MURRAY et al. (1989): Grad 1-4 25 2.7.2 Bewertungssystem nach MACALLISTER et al. (1995), modifiziert nach LUNDBERG (1995): Werte I-IV 26 2.8 Histologische Gastritis-Klassifizierung nach dem aktualisierten Sydney-System aus der Humanmedizin nach STOLTE et al. 1997 26 2.8.1 Entstehung des Sydney-Systems nach STOLTE et al. 1990 (STOLTE 1997) 26 2.8.2 Das aktualisierte Sydney-System nach STOLTE et al. 1997 (STOLTE 1997) 27 2.8.2.1 Klassifikation 27 2.8.2.2 Graduierung der morphologischen Variablen im histologischen Bild 28 2.8.2.3 Zu graduierende Variable 29 2.8.2.3.1 Helicobacter pylori – Dichte 29 2.8.2.3.2 Grad der chronischen Entzündung 29 2.8.2.3.3 Graduierung der Aktivität der Gastritis 30 2.8.2.3.4 Atrophie des Drüsenkörpers 31 2.8.2.3.5 Intestinale Metaplasie 31 2.8.2.4 Andere, nicht zu graduierende Variable 33 2.8.2.4.1 Oberflächenepithel, Schleimdepletion und Erosion 33 2.8.2.4.2 Lymphfollikel 33 2.8.2.4.3 Foveoläre Hyperplasie 34 2.8.2.5 Gastritiden 34 3 Eigene Untersuchungen 37 3.1 Material und Methodik 37 3.1.1 Patientenmaterial und Anamnese 37 3.1.2 Makroskopische Befundbeschreibung des eröffneten Magens 38 3.1.3 Gewebeproben 38 3.1.3.1 Probenentnahme und Bearbeitung 38 3.1.3.2 Histologische Bearbeitung der Proben 40 3.1.3.2.1 Hämatoxylin-Eosin-Färbung 41 3.1.3.2.2 Warthin-Starry-Färbung 41 3.1.3.2.3 Immunhistochemie (IHC) 41 3.1.4 Mikroskopische Befundbeschreibung nach dem aktualisierten Sydney-System nach STOLTE et al. 1997 42 3.1.5 Nachweis von Helicobacter-like-Organismen 43 3.1.5.1 Histologischer Nachweis 43 3.1.5.2 Molekularbiologische Testmethoden 43 3.1.6 Humanmedizinische Befundbeschreibung der ätiologischen Diagnosen nach dem aktualisierten Sydney-System (STOLTE et al. 1997) 45 3.2 Ergebnisse 46 3.2.1 Makroskopische Befundbeschreibung nach MURRAY et al. 1989 und nach MACALLISTER et al. 1995 46 3.2.2 Makroskopische Befundbeschreibung nach STOLTE et al. 1993 48 3.2.3 Mikroskopische humanmedizinische Beurteilung nach STOLTE et al. 1997 51 3.2.3.1 Histologische Beurteilung nach dem humanmedizinischen aktualisierten Sydney-System (STOLTE et al. 1997) 51 3.2.3.2 Histologische Beurteilung anhand der Hämatoxylin-Eosin- Färbung (HE) nach dem aktualisierten Sydney-System aus der Humanmedizin (STOLTE et al. 1997) 53 3.2.3.3 Histologische Beurteilung anhand der Warthin-Starry-Färbung und der immunhistochemische-Reaktion nach dem aktualisierten Sydney-System aus der Humanmedizin (STOLTE et al. 1997) 65 3.2.4 Histologische Befunde in der Drüsenschleimhaut bei Pferden mit Nachweis von Helicobacter-like-Organismen 66 3.2.5 Ätiologische Diagnosen nach dem aktualisierten Sydney-System aus der Humanmedizin (STOLTE et al. 1997) 76 3.2.6 Zusammenhang der makroskopischen und mikroskopischen Befunde 77 3.3 Ergebnisse der PCR 78 4 Diskussion 79 4.1 Methodik und Durchführung 79 4.2 Makroskopische Befunde 82 4.3 Mikroskopische Befunde 85 4.4 Helicobacter-like-Organismen, Häufigkeit, Lokalisation und Kolonisationsdichte 88 4.5 Einfluss der Besiedlung mit Helicobacter-like-Organismen auf die Gastritis und deren Behandlung 92 4.6 Ätiologische und deskriptive Diagnosen nach humanmedizinischen Kriterien 92 4.7 Veterinärmedizinische makroskopische Bewertungssysteme 95 4.8 Das humanmedizinische aktualisierte Sydney-System nach STOLTE et al. 1997 96 5 Zusammenfassung 99 6 Summary 101 7 Literaturverzeichnis 103 8 Anhänge 121 8.1 Anamneseprotokoll 121 8.1.1 Lebensalter, Geschlecht und Rasse der 60 Pferde 123 8.1.2 Klinische Diagnosen der 60 Pferde 125 8.1.3 Anamnese der 60 Pferde 128 8.2 Makroskopische Befundbeschreibung des eröffneten Magens nach STOLTE et al. (1993) 134 8.3 Makroskopische Klassifikation nach MURRAY et al. (1989) 136 8.4 Makroskopische Klassifikation nach MACALLISTER et al. (1995) modifiziert nach LUNDBERG (1995) 137 8.5 Makroskopische Beurteilung (Grading) 139 8.6 Graduierung nach dem aktualisierten Sydney-System STOLTE et al. (1997), im Vergleich dazu die makroskopische Beurteilung der Pars glandularis nach MACALLISTER et al. (1995) 141 8.7 Ätiologische oder deskriptive Diagnosen der 60 Pferde in der Pars glandularis der großen Kurvatur und dem Pylorus 146 9 Danksagungen 147

Name: The Effect of Facilitating Kinesio Taping of lower scapula fixators on pain threshold of trigger points in the m. trapezius pars descendens Objectives: This study is a pilot study. The goal of this study is to determine effects of Facilitating Kinesio Taping of lower scapula fixators on painfulness of trigger points in the m. trapezius pars descendens. Methods: The study took place in a private medical office with thirteen patients. All of these patients were physically examined using standard tests of physiotherapy. Patients were measured using a pressure algometer to assess trigger points as painful. They reported the intensity of pain on VAS. The places of measurement were trigger points one and two in the muscle according Travell and Simons. Data were analyzed using the statistical program SPSS 15.0 and Microsoft Office Excel. Results: This study had three hypotheses. In the case of the first hypothesis, I concluded that KT has an effect on the pain threshold and its application will reduce the pain threshold in m.trapezius pars descendens. Statistical significance was the value of p = 0.03 and p = 0.011, the value of material significance (101.31 kPa and 106.7 kPa) confirmed my theory that after KT will increase the pressure of 100 kPa in the TrP1 and TrP2. In the second hypothesis, it...

Made available in DSpace on 2016-04-28T14:16:34Z (GMT). No. of bitstreams: 1 Veranice Canato.pdf: 2119970 bytes, checksum: 0b3e2b259a68a1ec4980cdecd8d345a1 (MD5) Previous issue date: 2008-10-02 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / In the year of 1604, with the objective to produce a theory, that would explain the refraction of light of celestial bodies and solve the existing problems in the observation of solar eclipses through camera obscura, Johannes Kepler published Ad VItellionem Paralipomena, quibus Astronomiae pars Optica Traditvr. Paralipomena has been raising the attention of history of science researchers since the first decades of the twentieth-century, and its classification, as either a continuity or a break with the treatises of optics developed during the Middle Ages, has become a controversial theme. Different aspects in this debate lead to a comprehension of Kepler's work as an appreciation of several studies of optics, astronomy and natural magic available at the end of sixteenth- century. Several studies available in Kepler s times, which probably contributed for his solution of the problems with the camera obscura, are presented in this dissertation in an attempt to show that Kepler s elaboration of his camera obscura theory, presented in chapter second of Paralipomena, is a consequence of this appreciation / Com o objetivo de apresentar teorias capazes de explicar a refração da luz nos corpos celestes e de solucionar problemas nas observações de eclipses solares com câmaras escuras. Johannes Kepler (1571-1630) publicou, em 1604, o seu Ad VItellionem Paralipomena ,quibus Astronomiae pars Optica Traditvr. Esse livro vem despertando a atenção de pesquisadores em história da ciência desde as primeiras décadas do século XX e se constituiu como objeto de um polêmico debate em torno de sua classificação como uma continuidade ou uma ruptura com os tratados ópticos desenvolvidos no medievo. Os diferentes aspectos destacados nesse debate possibilitam uma compreensão do trabalho de Kepler como uma apreensão dos diversos estudos de óptica, de astronomia e de magia natural que circulavam no final do século XVI. Nesta dissertação, procuramos mostrar que a elaboração de sua teoria para a câmara escura, apresentada no segundo capítulo do Paralipomena, é uma conseqüência dessa apreensão. Para tal, procuramos analisar vários trabalhos que circulavam à época de Kepler e que possivelmente contribuíram para a sua solução dos problemas da câmara escura

The midbrain dopamine system is involved in many aspects of purposeful behaviour and, when compromised, can have devastating effects on movement and cognition as seen in diseases like Parkinson's. In the healthy brain, dopamine neurons are thought to play particularly important roles in learning by signalling errors in reward prediction. The objective of this thesis was to investigate the diversity in the functional properties of the midbrain dopamine system, and how this is altered through genetic variation of relevance to Parkinson's and development of cell phenotype. This objective was addressed with a combination of behavioural experiments, in vivo single-cell recording and labelling (both in anaesthetised as well as awake rodents), immunofluorescence labelling, retrograde tracing and stereology. In a first set of experiments, it was demonstrated that chronic as well as acute genetic challenges can alter the firing patterns of midbrain dopamine neurons. Using a novel bacterial artificial chromosome-transgenic rat model, it was shown that the R1441C mutation in human leucine-rich repeat kinase 2, which is linked to Parkinson's, leads to motor deficits and an age-dependent reduction in the in vivo firing variability and burst firing of substantia nigra pars compacta (SNc) dopamine neurons. These findings help reveal processes of early, pre-degenerative dysfunction in dopamine neurons in Parkinson's. Similar effects on firing variability and burst firing of SNc dopamine neurons were found in a mouse model with conditional knock- out of the transcription factors Forkhead box A1 and A2 (FoxA1/2) in midbrain dopamine neurons. These findings indicate that FoxA1/2 are not only crucial for the early development of dopamine neurons, but also their function in the mature brain. In a second set of experiments in wildtype mice, it was demonstrated that midbrain dopamine neurons (located in SNc and ventral tegmental area) show diverse expression of the molecular markers Calbindin, Calretinin, Aldh1a1, Sox6, Girk2, SatB1 and Otx2. It was found that selective expression of these markers is of use for discriminating between midbrain dopamine neurons that project to dorsal striatum or nucleus accumbens. To elucidate whether the diverse molecular marker expression would map onto dopamine neurons whose firing correlates with distinct behavioural events, midbrain dopamine neurons were recorded and labelled in head-fixed awake mice either exposed to neutral sensory stimuli or performing a classical conditioning paradigm. The population activity of midbrain dopamine neurons was not modulated by neutral sensory stimuli. Interestingly, fewer than 50% of identified dopamine neurons showed phasic firing increases following reward- predicting cue and/or reward delivery, despite the common assumption that most (if not all) midbrain dopamine neurons signal reward prediction errors. Instead, firing was modulated by other explanatory factors, such as licking, or showed no modulation during the task. Response types of midbrain dopamine neurons were not correlated with their anatomical location nor the selective or combinatorial expression of the markers Aldh1a1, Calbindin and Sox6. In conclusion, the first set of experiments identified how different genetic burdens can alter the in vivo firing of midbrain dopamine neurons, and provide new insights into how circuits can change in pathological or compensatory ways at early disease stages in Parkinson's. The second set of experiments revealed striking heterogeneity of midbrain dopamine neurons in the intact system, and established further a functional diversity in the response types of identified midbrain dopamine neurons that is only partially consistent with canonical reward prediction error signalling.

Les ganglions de la base, un ensemble de noyaux sous-corticaux interconnectés, sont impliqués dans l'élaboration, le contrôle et la mémorisation de comportements cognitivo-moteurs. L'une des principales structures de sortie de ce réseau, la substance noire réticulée (SNr), intègre les différentes informations neuronales puis les transmet au cortex via un relais thalamique. Cependant, cette transmission nécessite une régulation fine de l'activité neuronale de la SNr car celle-ci exerce une inhibition constante de ces structures cibles en raison de son activité GABAergique spontanée. Parmi les acteurs de cette régulation, le glutamate et le GABA sont à l'origine d'un équilibre fin entre excitation et inhibition des neurones nigraux. De nombreuses études se sont intéressées aux mécanismes de régulation de l'activité neuronale de la SNr mais, paradoxalement, aucune ne s'est intéressée au rôle des astrocytes. L'objet de ce travail de thèse a donc été d'étudier les relations entre neurones et astrocytes au sein de la SNr, afin de définir une potentielle implication des astrocytes dans la régulation de l'activité neuronale de cette structure. Nous avons étudié les excitabilités calciques des astrocytes et électriques des neurones grâce aux techniques d'imagerie calcique et de patch-clamp, dans un modèle de tranche parasagittale de cerveau de rat préservant les connexions subthalamo-nigrales et pallido-nigrales. Nous avons ainsi montré que les astrocytes nigraux possèdent une activité calcique spontanée, à la fois autonome et dépendante des libérations toniques de glutamate et de GABA. D'autre part, nous avons mis en évidence que l'activité de ces cellules est modulée par la stimulation à haute fréquence du noyau sous-thalamique. Nous avons montré qu'en retour, ces activités calciques spontanées astrocytaires sont impliquées dans la régulation de la fréquence de décharge des neurones de la SNr. Enfin, nous avons mis en évidence que la recapture astrocytaire du glutamate, et probablement du GABA, intervient également dans la régulation de l'activité de décharge neuronale nigrale. En conclusion, ce travail met en évidence une communication bidirectionnelle entre les neurones et les astrocytes de la SNr. Cette communication semble jouer un rôle important dans la régulation de l'activité de cette structure. / Basal ganglia, a set of interconnected nuclei, are implicated in the elaboration, control and memorization of cognitive-motor behaviors. One of the main output structure of this network, the substantia nigra pars reticulata (SNr), integrates and conveys neuronal information to cortical areas via a thalamic relay. However, this transmission requires an accurate regulation of the SNr neuronal activity since this structure inhibits its targets due to its spontaneous GABAergic activity. Among the different actors of this regulation, glutamate and GABA provide a tight balance between excitation and inhibition of the SNr neuronal activity. Several studies have explored the different mechanisms involved in this regulation but paradoxically, none concerned the astrocyte functions. In this work, our aim was to study astrocyte-neuron relations in order to define a potential astrocyte implication in the regulation of the neuronal activity in the SNr. We studied calcium and electrical activities of astrocytes and neurons using calcium imaging and patch-clamp techniques in parasagittal rat brain slices, conserving subthalamo- and pallido-nigral projections. We showed that astrocytes in the SNr displayed spontaneous calcium activities, both dependent and independent of glutamatergic and GABAergic tonic neuronal transmissions. Moreover, we showed that astrocytes calcium activities were regulated by the subthalamic nucleus high frequency stimulation. Our results revealed that, in turn, astrocytes calcium activities were involved in the regulation of the neuronal firing rate. Finally, we showed that astrocyte glutamatergic, and maybe GABAergic, reuptake was involved in the regulation of the neuronal firing rate. To conclude, this study revealed a bidirectional communication between astrocytes and neurons in the SNr. This communication seems to be important in the regulation of the activity in this structure.