The development of the animal after birth is marked by complex changes. Certain periods are particularly important and have been defined as "critical periods" (Krecek, 1971). Two processes are important to the survival of the animals during these times. The process of "adaptation" involves the maturation of specific physiological systems according to the needs of the neonatal animal, and is dictated by the external environment. The process of "tolerance" renders the neonate relatively unresponsive to a stressor as compared to the adult and protects the animals from over-responding the depleting vital resources until it is physiologically mature. An example of tolerance is the resistance to anoxia of immature neonates. The newborn pig has a high rate of mortality. The number of pigs born 114 days after conception represent only about 55% of the original ova released. Besides having a large number of embryo losses during the gestation period, 13-25% of the live born piglets die before weaning as shown in Table I. The low viability of the neonatal piglets is undoubtedly related to their inability to maintain homeostasis during stress. The sympathetic division of the autonomic nervous system is a major coordinator of homeostasis. Therefore, a study of the development of the sympathetic nervous system could provide some clues to explain the high mortality rate of the newborn pigs. Since the coordinating ability of the sympathetic nervous system is not only dependent on the maturity of the system, but also on the development of the effector organs and their responsiveness to activation, it is logical to examine their relative development.

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Os macacos Cebus apella são hábeis com suas mãos e capazes de utilizar ferrementas (paus e pedras) para resolver problemas, podendo ser treinados como assistentes de pessoas quadriplégicas. São escassas ainda as informações em neuroanatomia desses primatas, o que motiva a presente pesquisa, cujo propósito é o de enfocar a morfologia externa e interna do tronco encefálico. Foram estudados 20 espécimes do macaco Cebus apella que já estavam fixados com formol a 10%, pertencentes ao acervo de pesquisa do laboratório de Anatomia da Universidade Federal de Uberlândia. Após isolamento do encéfalo e remoção das meninges procedeu ? se ao estudo da superfície externa em 14 peças. A dissecção por técnica usual preservou características morfológicas da superfície e origem aparente de nervos cranianos, que foram identificados. Em análise macroscópica, o tronco encefálico mostra ? se bem desenvolvido destacando ? se ainda em sua face lateral a origem aparente do nervo trigêmeo e os pedúnculos cerebelares médios, bem evidentes. Na face dorsal, em relação ao IV ventrículo identificam ? se os véus medulares superior e inferior, bem como o sulco mediano e a eminência medial. Os pedúnculos cerebelares superior e inferior também são bem destacados. Na medula oblonga são identificados, entre outros, os relevos correspondentes às olivas e às pirâmides, além da fissura mediana anterior e a região da decussação das pirâmides, Nem sempre são nítidos o sulco bulbo ? pontino e o forame cego. Os fascículos grácil e cuneiforme são bastante desenvolvidos bem como os tubérculos correspondentes. Para os estudos das estruturas internas do tronco encefálico, 6 peças, já fixadas, foram congeladas com nitrogênio líquido e cortadas no criostato entre ?27º C e ? 30º C, seguindo ? se a feitura de cortes transversais, em seis níveis (colículos superior e inferior, origem aparente do nervo trigêmeo, porções superior, média e inferior da oliva, e decussação das pirâmides), com espessura de 60 µc, corados segundo o método de Mulligan. As estruturas evidenciáveis são descritas com detalhes comparando ? se os dados obtidos com os da literatura consultada. Os termos anatômicos foram referidos segundo a Terminologia Anatômica Internacional, 1ª edição brasileira ? 2001, Ed. Manole Ltda. / The Cebus apella monkey are able to use their nands and to use tools like woods and stones to solve problems. They can be trained to act as quadriplégicas people?s assistants. The Neuroanatomy information about these primates are little, that?s the reason for this research and its purpose is to accomplish a macroscophial anatomic study of encephalic trunk external and internal surface structure. It was studied Cebus apella monkeu 20 especimens that was already fixed on 10% formaldehyde. These monkeys are from research?s heap of Universidade Federal de Uberlândia. The monkey encephalon were removed using an osteótomo. After removing the meninges, theirs external surface study was started on 14 of them. The dissection using usual technique could preserve the morphological characteristics of the surface and cranial nerve apparent origim, that could be identified too. Under a macroscophical analysis, the encephalic trun looks very elaborated and the trigemini nerve and pedunculus cerebellaris aparent origin, very evident, was stood out in its lateral face. In the dorsal face, in relation to fourth ventricle, the inferior and superior velum medullare could be identified as well as the sulcus medianus and the eminentia medialis. The superior pedunculus cerebellaris, as well as the inferior ones, were very stood out too. On the medulla oblongata were identified, beyond others, the relieves corresponding to the oliva and the decussatio pyramidum region. The sulcus bulbus ? pons and the foramen caecum not always are bright. The fasciculus gracilis, as well as the cuneatus ones, are very elaborated as well as the corresponding tuberculuns.The brain stem internal structure study 6 already fixed pieces were froze with liquid nitrong and cut in criostato, under the temperature between ?27ºC and ? 30º C. After this, transversal cuts were made on 6 levels (superior and inferior nerve trigemini aparent origin, olivas superior, medium and inferior portion and decussatio pyramidum), with the thickness of 60µc, roddy according to the Mulligan method. The evidentiable structures are described in details comparing data obtained from the consulted literature. The anatomic terms were aforesaid according to Terminologia Anatômica Internacional, 1ª edição brasileira ? 2001, Ed. Manole Ltda.

A doença de Parkinson (DP) apresenta declínio da capacidade respiratória. Estudo utilizando um modelo de DP induzido pela injeção de 6-hidroxidopamina (6-OHDA) no estriado mostrou redução no número de neurônios envolvidos no controle da respiração. O objetivo desse estudo foi avaliar alterações gliais no núcleo retrotrapezóide (RTN), núcleo do trato solitário, complexo pré-Bötzinger e grupamento respiratório ventrolateral rostral (rVRG) utilizando o mesmo modelo experimental. Em ratos Wistar que receberam a injeção de 6-OHDA bilateralmente no estriado observou-se redução na imunorreatividade para proteína ácida fibrilar glial em astrócitos no rVRG a partir de 30 dias, no RTN a partir de 40 dias e nas demais regiões a partir de 60 dias. Ainda, observamos o aumento da proteína ligante de actina cruzada em microglias na região do RTN aos 30 e 40 dias. Nossos dados sugerem que a redução astrocitária contribui para as alterações respiratórias observadas neste modelo experimental e a presença de neuroinflamação no RTN pode contribuir para a perda celular nesta região. / Parkinson\'s disease (PD) has a decline in respiratory capacity. A study using a model of PD induced by the injection of 6-hydroxydopamine (6-OHDA) in the striatum showed a reduction in the number of neurons involved in the control of breathing. The aim of this study was to evaluate glial changes in the retrotrapezoid nucleus (RTN), nucleus of the solitary tract, pre-Bötzinger complex and rostral ventral respiratory group (rVRG) using the same experimental model. Wistar rats that received bilateral 6-OHDA injection in the striatum present a reduction in immunoreactivity for glial fibrillary acidic protein in astrocytes in the rVRG from 30 days, in the RTN from 40 days and in the other regions from 60 days. We also observed an increase of the Ionized calcium binding adaptor molecule 1 in microglia in the region of the RTN at 30 and 40 days. Our data suggest that astrocytic reduction contributes to the respiratory changes observed in this experimental model and the presence of neuroinflammation in the RTN may contribute to the cellular loss in this region.

The relationship between the endocannabinoid system in the renal medulla and the long-term regulation of blood pressure is not well understood. To investigate the possible role of the endocannabinoid system in renomedullary interstitial cells, mouse medullary interstitial cells (MMICs) were obtained, cultured and characterized for their responses to treatment with a selective inhibitor of fatty acid amide hydrolase (FAAH), PF-3845. Treatment of MMICs with PF-3845 increased cytoplasmic lipid granules detected by Sudan Black B staining and multilamellar bodies identified by transmission electron microscopy. HPLC analyses of lipid extracts of MMIC culture medium revealed a 205nm-absorbing peak that showed responsiveness to PF-3845 treatment. The biologic activities of the PF-3845-induced product (PIP) isolated by HPLC were investigated in anesthetized, normotensive surgically-instrumented mice. Intramedullary and intravenous infusion of PIP at low dose rates (0.5-1 AU/10 min) stimulated diuresis and natriuresis, whereas at higher doses, these parameters returned toward baseline but mean arterial pressure (MAP) was lowered. Whereas intravenous bolus doses of PIP stimulated diuresis, GFR and medullary blood flow (MBF) and reduced or had no effect on MAP, an intraperitoneal bolus injection of PIP reduced MAP, increased MBF, and had no effect on urinary parameters. Genetic or pharmacological ablation of the cannabinoid type 1 receptors in mice completely abolished the diuretic and vasodepressor properties of intramedullary infused PIP, suggesting that the PF-3845-induced product requires the presence of CB1 receptors in order to elicit its renal effects. In a radioactive competition binding assay, using Chinese hamster ovary cells expressing CB1 receptors, PIP successfully displaced the CB1 selective inverse agonist [3H] SR141716A, revealing that the lipid extract was able to compete for binding to CB1 receptors. Finally, we investigated the tubular location of diuretic activity that the PF-3845-induced lipid fraction exhibits. In a renal function in vivo experiment, we pre-treated anesthetized mice with an intramedullary infusion of one of four well-known diuretics. This procedure was followed by an intramedullary infusion of PIP (1AU). Only inhibition of the proximal tubule sodium reabsorption diminished the diuretic activity of the PF-3845-induced product, suggesting that the lipid fraction requires a physiologically intact proximal tubular reabsorption mechanism for it to produce diuresis. These data support a model whereby PF-3845 treatment of MMICs results in increased secretion of a neutral lipid which acts directly to promote diuresis and natriuresis and indirectly through metabolites to produce vasodepression. Efforts to identify the structure of the PF-3845-induced lipid and its relationship to the previously proposed renomedullary antihypertensive lipids are ongoing.

Mevinphos (Mev) is an organophosphate insecticide that acts on the rostral ventrolateral medulla (RVLM), the origin of sympathetic vasomotor tone, to induce cardiovascular responses. This study investigated the role of Trk (tropomyosin-related kinase) (receptor form) or Src (non-receptor form) tyrosine kinase at the RVLM in Mev-induced cardiovascular responses. Bilateral microinjection of Mev (10 nmol) into the RVLM elicited two distinct phases of cardiovascular responses, designated Phase I (sympathoexcitatory) and Phase II (sympathoinhibitory) Mev intoxication. Western blot assay showed that whereas p-Trk490 was increased during Phase I, p-Src416 was increased only during Phase II Mev intoxication. Interestingly, application of a Trk specific inhibitor (K252a; 1 pmol) or Src specific inhibitor (SU6656; 100 pmol) into the bilateral RVLM blunted the Mev-elicited sympathoexcitatory or sympathoinhibitory effect, respectively. Besides, K252a was limited to block NOS I protein expression in the RVLM during Mev intoxication, SU6656 only inhibited NOS II protein expression in the RVLM during Mev intoxication. We conclude that Trk tyrosine kinase (p-Trk490) in the RVLM participates in the Phase I cardiovascular responses during Mev intoxication, Src tyrosine kinase (p-Src416) in the RVLM participates in the Phase II cardiovascular responses associated with Mev intoxication.

A doença de Parkinson (DP) apresenta declínio da capacidade respiratória. Estudo utilizando um modelo de DP induzido pela injeção de 6-hidroxidopamina (6-OHDA) no estriado mostrou redução no número de neurônios envolvidos no controle da respiração. O objetivo desse estudo foi avaliar alterações gliais no núcleo retrotrapezóide (RTN), núcleo do trato solitário, complexo pré-Bötzinger e grupamento respiratório ventrolateral rostral (rVRG) utilizando o mesmo modelo experimental. Em ratos Wistar que receberam a injeção de 6-OHDA bilateralmente no estriado observou-se redução na imunorreatividade para proteína ácida fibrilar glial em astrócitos no rVRG a partir de 30 dias, no RTN a partir de 40 dias e nas demais regiões a partir de 60 dias. Ainda, observamos o aumento da proteína ligante de actina cruzada em microglias na região do RTN aos 30 e 40 dias. Nossos dados sugerem que a redução astrocitária contribui para as alterações respiratórias observadas neste modelo experimental e a presença de neuroinflamação no RTN pode contribuir para a perda celular nesta região. / Parkinson\'s disease (PD) has a decline in respiratory capacity. A study using a model of PD induced by the injection of 6-hydroxydopamine (6-OHDA) in the striatum showed a reduction in the number of neurons involved in the control of breathing. The aim of this study was to evaluate glial changes in the retrotrapezoid nucleus (RTN), nucleus of the solitary tract, pre-Bötzinger complex and rostral ventral respiratory group (rVRG) using the same experimental model. Wistar rats that received bilateral 6-OHDA injection in the striatum present a reduction in immunoreactivity for glial fibrillary acidic protein in astrocytes in the rVRG from 30 days, in the RTN from 40 days and in the other regions from 60 days. We also observed an increase of the Ionized calcium binding adaptor molecule 1 in microglia in the region of the RTN at 30 and 40 days. Our data suggest that astrocytic reduction contributes to the respiratory changes observed in this experimental model and the presence of neuroinflammation in the RTN may contribute to the cellular loss in this region.

Os macacos Cebus apella são hábeis com suas mãos e capazes de utilizar ferrementas (paus e pedras) para resolver problemas, podendo ser treinados como assistentes de pessoas quadriplégicas. São escassas ainda as informações em neuroanatomia desses primatas, o que motiva a presente pesquisa, cujo propósito é o de enfocar a morfologia externa e interna do tronco encefálico. Foram estudados 20 espécimes do macaco Cebus apella que já estavam fixados com formol a 10%, pertencentes ao acervo de pesquisa do laboratório de Anatomia da Universidade Federal de Uberlândia. Após isolamento do encéfalo e remoção das meninges procedeu ? se ao estudo da superfície externa em 14 peças. A dissecção por técnica usual preservou características morfológicas da superfície e origem aparente de nervos cranianos, que foram identificados. Em análise macroscópica, o tronco encefálico mostra ? se bem desenvolvido destacando ? se ainda em sua face lateral a origem aparente do nervo trigêmeo e os pedúnculos cerebelares médios, bem evidentes. Na face dorsal, em relação ao IV ventrículo identificam ? se os véus medulares superior e inferior, bem como o sulco mediano e a eminência medial. Os pedúnculos cerebelares superior e inferior também são bem destacados. Na medula oblonga são identificados, entre outros, os relevos correspondentes às olivas e às pirâmides, além da fissura mediana anterior e a região da decussação das pirâmides, Nem sempre são nítidos o sulco bulbo ? pontino e o forame cego. Os fascículos grácil e cuneiforme são bastante desenvolvidos bem como os tubérculos correspondentes. Para os estudos das estruturas internas do tronco encefálico, 6 peças, já fixadas, foram congeladas com nitrogênio líquido e cortadas no criostato entre ?27º C e ? 30º C, seguindo ? se a feitura de cortes transversais, em seis níveis (colículos superior e inferior, origem aparente do nervo trigêmeo, porções superior, média e inferior da oliva, e decussação das pirâmides), com espessura de 60 µc, corados segundo o método de Mulligan. As estruturas evidenciáveis são descritas com detalhes comparando ? se os dados obtidos com os da literatura consultada. Os termos anatômicos foram referidos segundo a Terminologia Anatômica Internacional, 1ª edição brasileira ? 2001, Ed. Manole Ltda. / The Cebus apella monkey are able to use their nands and to use tools like woods and stones to solve problems. They can be trained to act as quadriplégicas people?s assistants. The Neuroanatomy information about these primates are little, that?s the reason for this research and its purpose is to accomplish a macroscophial anatomic study of encephalic trunk external and internal surface structure. It was studied Cebus apella monkeu 20 especimens that was already fixed on 10% formaldehyde. These monkeys are from research?s heap of Universidade Federal de Uberlândia. The monkey encephalon were removed using an osteótomo. After removing the meninges, theirs external surface study was started on 14 of them. The dissection using usual technique could preserve the morphological characteristics of the surface and cranial nerve apparent origim, that could be identified too. Under a macroscophical analysis, the encephalic trun looks very elaborated and the trigemini nerve and pedunculus cerebellaris aparent origin, very evident, was stood out in its lateral face. In the dorsal face, in relation to fourth ventricle, the inferior and superior velum medullare could be identified as well as the sulcus medianus and the eminentia medialis. The superior pedunculus cerebellaris, as well as the inferior ones, were very stood out too. On the medulla oblongata were identified, beyond others, the relieves corresponding to the oliva and the decussatio pyramidum region. The sulcus bulbus ? pons and the foramen caecum not always are bright. The fasciculus gracilis, as well as the cuneatus ones, are very elaborated as well as the corresponding tuberculuns.The brain stem internal structure study 6 already fixed pieces were froze with liquid nitrong and cut in criostato, under the temperature between ?27ºC and ? 30º C. After this, transversal cuts were made on 6 levels (superior and inferior nerve trigemini aparent origin, olivas superior, medium and inferior portion and decussatio pyramidum), with the thickness of 60µc, roddy according to the Mulligan method. The evidentiable structures are described in details comparing data obtained from the consulted literature. The anatomic terms were aforesaid according to Terminologia Anatômica Internacional, 1ª edição brasileira ? 2001, Ed. Manole Ltda.

Doctor of Philosophy / Department of Anatomy and Physiology / Michael J. Kenney / It is well established that normal aging is associated with progressive increases in efferent sympathetic nerve discharge (SND). Type II diabetes, obesity, heart failure, and hypertension are pathologies that have been attributed to both the processes of aging and sympathetic dysfunction, exemplifying the importance of understanding central regulation of SND during aging. However, the central mechanisms mediating altered SND with advancing age remain unclear. The rostral ventral lateral medulla (RVLM) is a brainstem region critically involved in setting the basal level of sympathetic outflow and cardiovascular function. Indeed, the RVLM is the only presympathetic region that when bilaterally inactivated results in profound reductions in both SND and arterial pressure. Glutamatergic influences in RVLM activity are powerfully inhibited by tonic GABAergic neural inputs originating from the caudal ventral lateral medulla (CVLM); effects that are mediated by GABAA receptors located on presympathetic neuronal cell bodies within the RVLM. In the present study we proposed that reductions in GABA[subscript A] receptor subunit gene expression may reflect withdrawal of GABAergic tone in the RVLM thereby contributing to the basal sympathetic activation that occurs with advancing age. Therefore, the objective of the current study was to identify age-related changes in the constitutive expression of genes related to GABAergic and muscarinic, nicotinic and dopaminergic receptor systems due to their reported involvement in modulating GABA[subscript A] receptor function, in the RVLM of adult young (3-5 mo. old), middle-aged (12 mo. old), weight stable presenescent (24-25 mo. old) and senescent (>24 mo. old) Fischer 344 (F344) rats using a commercially available real-time PCR array. Real-time analysis revealed nonuniform and age-associated changes in the RVLM GABA, muscarinic, nicotinic and dopaminergic neurotransmitter gene expression profile between young and middle-aged F344 rats. Heterogeneous expression of genes related to these neurotransmitters was also observed between presenescent and senescent F344 rats. Our results suggest that potential changes in neurotransmitter synthesis and degradation, uptake, transport, signaling and receptor subunit composition may account for the sympathoexcitatory state that is commonly observed in the aged.

Ventrolateral medullary neurons have important roles in cardiorespiratory coordination. A rostral extension of the ventral respiratory column (RVRC), including the retrotrapezoid nucleus (RTN), has neurons responsive to local perturbations of CO2 / pH. Respiratory-modulated firing patterns of RVRC neurons are attributed to influences of more caudal (CVRC) neurons. These circuits remain poorly understood. This study addressed the hypothesis that both local interactions and influences from the CVRC shape rostral neuron discharge patterns and responses. Spike trains from 294 rostral and 490 caudal neurons were recorded with multi-electrode arrays along with phrenic nerve activity in 14 decerebrate, vagotomized cats. Overall, 214 rostral and 398 caudal neurons were respiratory-modulated; 124 and 95, respectively, were cardiac-modulated. Subsets of these neurons were evaluated for responses to sequential, selective, transient stimulation of central and peripheral chemoreceptors and arterial baroreceptors. In 5 experiments, Mayer wave-related oscillations (MWROs) in neuronal firing rates were evoked, enhanced, or reduced following central chemoreceptor stimulation. Overall, 174 of the rostral neurons (59.5%) had short- time scale correlations with other RVRC neurons. Of these, 49 triggered cross-correlograms with RVRC targets yielding 330 offset features indicative of paucisynaptic actions from a total of 2,884 rostral pairs evaluated. Forty-nine of the CVRC neurons (10.0%) were triggers in 142 CVRC-RVRC correlograms - from a total of 8,490 - with offset features indicative of actions on RVRC neurons. Correlation linkage maps support the hypothesis that local circuit mechanisms contribute to the respiratory and cardiac modulation of RVRC neurons and their responses to chemoreceptor and baroreceptor challenges.