There is a higher prevalence of hearing loss in children with diagnosed neurological disorders than the general paediatric population. It is therefore essential that these children have their hearing assessed. Conventional behavioural audiometry requires participation from the child, and in a majority of this population with neurological pathology this is not always possible owing to their neurocompromised state. These children will have to undergo objective testing, such as the Auditory Brainstem Response (ABR) in order to obtain estimated hearing thresholds, as this requires no active involvement from the patient. This study therefore aims to describe the audiological ABR findings in order to determine hearing function in this group and to establish a relationship between audiological ABR findings to behavioural audiometry findings where these exist in a group of neurologically disordered children in a tertiary hospital in South Africa. Methods: A retrospective review was conducted on 40 ABR patient records of children between the ages of 5 months and 10 years diagnosed with a neurological disorder. Behavioural audiometry results were then sought for these children, where these existed. Hearing status was described for each child per ear for both objective and behavioural results, and descriptive statistics were conducted. Results: 56.25 % (n=45) of ears in this study presented with normal hearing on ABR testing. No behavioural audiometry results were obtained in 72.5 % (n=58) of ears in this study. Results correlated between ABR and behavioural testing for only 7.5% (n=8) of ears tested and in all eight of these ears the hearing result was within normal hearing limits. Twelve and a half percent (n=10) of ears were misdiagnosed on behavioural testing. More premature infants were able to be tested behaviourally when compared to other pathologies. Cerebral palsy, Down’s Syndrome, prematurity and RVD were the pathologies in which the most hearing losses were diagnosed. Conclusions: Behavioural audiometry appears a largely unreliable method of hearing testing in children diagnosed with neurological disorders as results were obtained in only 27.5 % of the study sample; however it remains the gold standard in paediatric hearing testing in order to evaluate the entire auditory system and provides information on how a child processes sound, unlike ABR testing which only provides hearing information up to the auditory brainstem. This study highlights the high prevalence of hearing problems in children with neurological disorders and therefore the importance of hearing testing in this population. Hearing thresholds should be established for subsequent remediation via objective testing. Conditioning should continue simultaneously for a behavioural audiological test battery with adaptations for the child’s developmental ability.

Migraine is a frequent debilitating neurological disorder that is considered to be genetically complex with a multifactorial mode of inheritance. It has a high prevalence with approximately 18% of women and 6% of men suffering from the disorder. Migraine is characterized by severe head pain with associated nausea, emesis, photophobia, phonophobia, and neurological disturbances. The International Headache Society (IHS) has classified various types of migraine according to their clinical features. The two main subtypes of migraine are migraine without aura (MO), occurring in ~70-75% of migraineurs, and migraine with aura (MA) which occurs in ~25% of migraineurs. Some people experience both types of attack in their lives. While the precise pathogenesis of migraine is unknown, it is widely accepted that short-term alterations in neuronal activity occur in relation to the attack, along with temporary changes in the cerebral vasculature. Trigeminal nerve activation is also considered pivotal to progression of a migraine attack. Neurotransmitters, especially serotonin (5-hydroxytryptamine, 5-HT), platelet activation and sympathetic hyperactivity all appear to play a part, whether as part of the primary triggering event, or as a response mechanism. Migraine imparts a significant burden on society, both socially and financially. The World Health Organization has identified migraine among the world's top 20 leading causes of disability, with an impact that extends far beyond individual suffering. There is significant evidence from family and twin studies to indicate a strong genetic component to migraine. The current understanding of migraine is that it is a polygenic multifactorial disorder. It has been postulated that genetic factors set the individual migraine threshold, with environmental influences playing a modulating role. It is likely that many genes may provide an important although moderate contribution to an individual’s migraine susceptibility. The identification of migraine susceptibility genes has been the focus of substantial research to date and could eventually lead to improved treatments and greater understanding of the disorder. Several loci have shown promise, although these need to be followed up by both replication and functional studies to determine a definitive causative role. This research investigated the role of both hormonal and vascular related genes as candidate genes that may play a role in migraine susceptibility due to the well-known role of hormones and vascular changes in some migraineurs. The estrogen receptor (ESR) and progesterone receptor (PGR) genes are potential migraine candidates due to the recognized hormonal influence on migraine susceptibility. Migraines in women frequently occur during the childbearing years and are often influenced by significant hormonal milestones. The fluctuating hormone levels of the menstrual cycle have been implicated in migraine but a definitive role is yet to be established. It has been suggested that factors additional to circulating hormone levels may be at play. This research considered that variation in the ESR 1 and PGR genes may confer an increased migraine risk. To investigate the potential role of these genes in migraine, association studies investigating variants in ESR 1 and PGR were undertaken in two independent casecontrol cohorts. This was followed up by mutation screening and gene expression analysis in an effort to elucidate a functional role for these genes in the pathogenesis of migraine. Vascular genes also represent likely migraine candidates as alterations in both vascular function and cerebral blood flow are well known in migraine. Furthermore, cortical spreading depression (CSD), a depolarization wave that propagates across the brain cortex and has been speculated to cause the neurological symptoms that present in MA, has also been linked to vascular dysfunction. The methylenetetrahydrofolate reductase (MTHFR) and methionine synthase (MTRR) genes both play a role in vascular functioning and were thus considered potential migraine candidates for this study. Both are involved in the pathway of homocysteine metabolism. Impaired activity of these enzymes can lead to mild hyperhomocysteinemia which is believed to lead to oxidative arterial damage. This may in turn impact on migraine susceptibility, possibly through the activation of trigeminal fibres. The MTHFR 677T allele results in an amino acid change in the catalytic domain of the enzyme leading to mild hyperhomocysteinemia. This particular variant has been implicated in migraine in four separate studies. One of these studies also suggested a role for the MTHFR 1298C allele in migraine. This allele also results in an amino acid change and reduced enzyme activity. Similarly, the MTRR 66G allele results in an amino acid change and has been associated with reduced activity of MTRR and increased plasma homocysteine concentration. To investigate the role of the ESR 1, PGR, MTHFR and MTRR genes in migraine, samples from two large independent case control cohorts were investigated. Cohort 1 was comprised of 275 migraineur samples and 275 age, sex and ethnicity matched controls while cohort 2 comprised 300 cases and 300 matched controls. All individuals were collected at the Genomics Research Centre with migraine diagnosis undertaken by HIS criteria and migraine affected individuals designated as MO or MA. Results of analysis of ESR 1 indicated a positive association with migraine in the two large independent cohorts for the exon 8 G594A polymorphism (P = 0.003; P = 8x10-6). Similarly, the PGR analysis showed a positive association with migraine for the PROGINS allele (P = 0.02; P = 0.003). Results also showed that individuals with both ESR 1 and PGR susceptibility alleles were 3.2 times more likely to suffer migraine those those with no susceptibility alleles. As the ESR 1 variant is synonymous, a mutation analysis was undertaken in a small sub-sample of individuals carrying the susceptibility allele, but no mutations were detected in these particular samples. Detailed mutation analysis of ESR 1 in a larger study group may be warranted. An ESR 1 and PGR expression analysis by RT-PCR was undertaken to examine if there were any notable expression level changes in migraineurs versus controls and additionally whether the susceptibility genotypes influenced gene expression. Altered expression levels may point to a functional change in the gene. Although results did not show any significant difference in expression levels in the case/control group, nor any influence in gene expression conferred by the specific susceptibility genotypes, ESR 1 expression did appear to be down-regulated in the migraine group and more specifically in the migraine susceptibility genotype subgroup. A larger study group may therefore be warranted to detect any potential genuine changes in gene expression. Overall, these results suggested that these hormonal genes appear to play a role in migraine susceptibility, although further studies are needed to define this. Results of the MTHFR 677 analysis showed that the TT genotype was significantly associated with the MA subgroup in a joint analysis of the two independent cohorts (P = 0.004). Results of analysis of MTHFR 1298, which is tightly linked to the 677 locus, showed a significant association in female migraineurs (P = 0.009). Similarly, results of the MTRR analysis also showed a significant difference between the female case and control groups with the G allele over-represented in female migraineurs (P = 0.022) These results may indicate that a significant gender effect appears in this locus as well as the MTHFR 1298 locus although results may also be due to a larger number of female migraineurs conferring increased statistical power to the gender subgroup. Interaction analysis of the MTHFR 1298 locus and the MTRR locus showed that females who carried both variants under a recessive model were 5 times more likely to suffer migraine those those with no susceptibility genotypes. Overall these results indicated that these vascular genes appear to play a role in migraine susceptibility. The final study focused on 6 genetic variants that had shown a positive association with migraine and/or MA in the same large association population analysed in this research. The aim of this study was to provide preliminary data on the potential role of genetic profiling in migraine. Using the genotypic data to create vascular and hormonal risk profiles based on positive association and interaction of MTHFR 677 T and ACE D alleles, and MTHFR 1298 AA and MTRR GG genotypes as vascular variants; and positive association and interaction of ESR 1 594 A and PGR PROGINS as hormonal variants, this study was able to demonstrate the relevance of genetic risk profiling to migraine. Results showed a significantly higher proportion of individuals with at least one genetic risk profile in the migraine group compared to those in the control group (P = 6 x 10-6). Individuals who possessed either the vascular and/or hormonal genetic risk profile were 8.6 times more likely to suffer from migraine than those who possessed a ‘no risk’ profile. This indicated a greater effect than the individual effect of each of these variants. Furthermore individuals who possessed a vascular or both risk profiles were more likely to suffer nausea, emesis, phonophobia and photophobia, and have a mother who also suffered migraine. Overall, the genetic profiling approach provided interesting preliminary data on migraine susceptibility and indicated that such an approach may prove very useful for migraine diagnosis, particularly when all migraine genes have been identified. In conclusion this study provided the first indication that hormone receptor genes play a role in migraine susceptibility. Hormones have long been considered to play a role in the disorder but this study has provided the first molecular evidence to support this premise. In addition, this study showed that vascular related genes also play a role in migraine susceptibility. Finally, this study has clearly shown that migraine is a complex disorder involving multiple genes. Although a number of studies have implicated neurotransmitter related genes in the disorder, the present study is the first to show that both vascular and hormonal genes also play a role in migraine susceptibility. Thus there now appear to be three classes of genes that affect migraine susceptibility and although this study has implicated new variants, the preliminary genetic profiling study has shown that not all predisposing variants involved in the disorder have been defined.

No description available.

No description available.

No / A neurological disorder is any disorder or abnormality in the nervous system. Among different neurological disorders, Alzheimer’s disease (AD) is recognized as the sixth leading cause of death globally. Considerable research has been conducted to find pioneer treatments for this devastating disorder among which cell therapy has attracted remarkable attentions over the last decade. Up to now, targeted differentiation into specific desirable cell types has remained a major obstacle to clinical application of cell therapy. Also, potential risks including uncontrolled growth of stem cells could be disastrous. In our novel protocol, we used basal forebrain cholinergic progenitor cells (BFCN) derived from human chorion-derived mesenchymal stem cells (hC-MSCs) which made it possible to obtain high-quality population of cholinergic neurons and in vivo in much shorter time period than previous established methods. Remarkably, the transplanted progenitors fully differentiated to cholinergic neurons which in turn integrated in higher cortical networks of host brains, resulting in significant improvement in cognitive assessments. This method may have profound implications in cell therapies for any other neurodegenerative disorders. / This work was carried outwithin the framework of a collaborative project (Project Grant No. 94-02-30-25922) by the School of Medicine, Iran University of Medical Sciences, (Project Grant No. REP209) council for stem cell sciences and technologies (Presidency of the Islamic Republic of Iran, vice-presidency for science and technology), and Iran National Science Foundation (INSF).

Background Creutzfeldt–Jakob disease is a rare and rapidly fatal neurodegenerative disease. Since clinicians may see only very few cases during their professional career, it is important to be familiar with the clinical presentation and progression, to perform appropriate investigations, and allow for quick diagnosis. Case presentation A 73-year-old British Caucasian woman presented with acute confusion of 2 weeks’ duration on a background of low mood following a recent bereavement. Her symptoms included behavioral change, visual hallucinations, vertigo, and recent falls. She was mildly confused, with left-sided hyperreflexia, a wide-based gait, and intention tremor in her left upper limb. Initial blood tests, computed tomography, and magnetic resonance imaging of her brain showed no significant abnormality. Following admission, she had rapid cognitive decline and developed florid and progressive neurological signs; a diagnosis of prion disease was suspected. A lumbar puncture was performed; cerebrospinal fluid was positive for 14–3-3 protein, real-time quaking-induced conversion, and raised levels of s-100b proteins were detected. An electroencephalogram showed bilateral periodic triphasic waves on a slow background. The diagnosis of probable Creutzfeldt–Jakob disease was made. Conclusions This case report highlights key features in the initial presentation and clinical development of a rare but invariably rapidly progressive and fatal disease. It emphasizes the importance of considering a unifying diagnosis for multifaceted clinical presentations. Although it is very rare, Creutzfeldt–Jakob disease should be considered a diagnosis for a mixed neuropsychiatric presentation, particularly with rapid progressive cognitive decline and development of neurological signs. However, to avoid overlooking early signal change on magnetic resonance imaging, it is important to take diffusion-weighted magnetic resonance imaging for all patients with neuropsychological symptoms. Importantly, early diagnosis also ensures the arrangement of suitable contamination control measures to minimize the risk of infection to health care professionals and other patients.

Funktionella neurologiska symtom är vanliga och funktionsnedsättande symtom som ofta anses svårbehandlade. En vanlig förklaringsmodell har varit att den drabbade varit med om något stressande och traumatiskt som lett till kroppsliga symtom. Denna förklaringsmodell leder till frågan om psykologisk behandling med fokus på trauma kan påverka funktionella neurologiska symtom. En systematisk litteraturöversikt, i enlighet med riktlinjer från Statens beredning för medicinsk och social utvärdering, har genomförts för att undersöka om psykologisk traumabehandling med kognitiv beteendeterapi och Eye Movement Desensitization and Reprocessing Therapy kan minska funktionella neurologiska symtom vid symtom på komorbid posttraumatiskt stressyndrom. Resultaten av litteraturöversikten består av totalt 10 artiklar, merparten fallstudier. Slutsatsen av litteraturöversikten tyder på att den forskning som gjorts visar på minskning av funktionella neurologiska symtom efter behandling av symtom på posttraumatiskt stressyndrom. Detta forskningsområde är dock väldigt litet och består främst av fallstudier med något bristande kvalitet. Trots detta anser vi att det finns underlag för att rekommendera att det bör finnas ett fokus på erfarenheter av trauma vid bedömning av funktionella neurologiska symtom.

Made available in DSpace on 2014-12-17T14:13:20Z (GMT). No. of bitstreams: 1 CarlosNA.pdf: 2422732 bytes, checksum: f5d47defbd8e5b492fe5d2975c8286ee (MD5) Previous issue date: 2006-12-28 / Innumerable studies have focused been reported on the sleep spindles (SS), Sharp Vertex Waves (SVW) and REM, NREM Sleep as indicators interpreting EEG patterns in children. However, Frequency and Amplitud Gradient (FAG) is rarely cited sleep parameter in children,that occurs during NREM Sleep. It was first described by Slater and Torres, in 1979, but has not been routinely evaluated in EEG reports. The aim of this study was to assess the absence of SS, SVW and FAG, as an indication of neurological compromise in children. The sample consisted of 1014 EEGs of children referred to the Clinical Neurophysiology Laboratory, Hospital Universit?rio de Bras?lia (HUB), from January 1997 to March 2003, with ages ranging from 3 months to 12 years old, obtained in spontaneous sleep or induced by choral hydrate. The study was transversal and analytical, in which, visual analysis of EEG traces was perfumed individually and independently by two electroencephalographers without prior knowledge of the EEG study or neurological findings. After EEG selection, the investigators analyzed the medical reports in order to define and correlate neurological pattern was classified according to the presence or absence of neurological compromise, as Normal Neurological Pattern (NNP), and Altered Neurological Pattern (ANP) respectively. From the visual analysis of the EEG(s), it was possible to characterize 6 parameters: 1- FAG present (64,1%); 2- FAG absent (35,9%); 3 - normal SS (87,9%); 4 - altered SS s (12,1%); 5 - normal SVW s (95,7%); 6 - altered SVW s (4,3%). The prevalence of well-formed FAG is found in the 3 months to 5 years age group in the children with NNF. FAG was totally absent from the age of 10 years. When comparing the three sleep graphielements, it was observed that SVW and SS were predominant in children with NNF. However, FAG absent was more prevalent in the ANF than in altered SS an SVW. The statistical analysis showed that there is a strong association of FAG absent, with isolated alteration, in ANF patients, in that the prevalence ratio was 6,60. The association becomes stronger when FAG absent + altered SS(s) is considered (RP= 6,68). Chi-square test, corrected by Yates technique, showed a highly significant relation for FAG &#961;= 0,00000001, for error X of 5%, or else the 95% confidence interval (&#961;<0,05). Thus, the FAG absent were more expressive in ANF patient than altered SS(s) and SVW(s). The association becomes stronger in order to establish a prognostic relation, when the FAG is combined with the SS. The results os this study allow us to affirm that the FAG, when absent at ages ranging from 3 months to 5 years , is an indication of neurological compromise. FAG is an age-dependent EEG parameter and incorporated systematically, in the interpretation criteria of the EEG of children s sleep, not only in the maturational point of view, but also neurological disturbances with encephalic compromise / In?meras pesquisas t?m focalizado periodicamente os fusos do sono (FS), as ondas agudas do v?rtex (OAV), o complexo K e o padr?o do sono REM e NREM como indicadores de avalia??o eletrencefalogr?fica da inf?ncia. O GFA ? um padr?o EEG do sono de crian?as que ocorre durante o sono NREM, raramente citado na literatura, e que, descrito pela primeira vez por Slater e Torres, em 1979, e n?o devidamente valorizado na rotina dos laudos EEG. Nas montagens referenciais ? caracterizado por uma progressiva diminui??o de voltagem e aumento de freq??ncia na dire??o p?stero-anterior. O objetivo desta tese, foi analisar o gradiente de freq??ncia e amplitude, um padr?o EEG do sono de crian?as que ocorre durante o sono NREM; estudar os fusos do sono(FS), ondas agudas do v?rtex (OAV), como indicadores de comprometimento neurol?gico. A popula??o de estudo constitui-se de 1014 EEG de crian?as atendidas no Laborat?rio de Neurofisiologia Cl?nica do Hospital Universit?rio de Bras?lia (HUB) no per?odo de janeiro de 1997 a mar?o de 2003, nas faixas et?rias de 3 meses a 12 anos de idade, obtidos em sono espont?neo ou induzido por hidrato de cloral. O tipo de ensaio foi transversal-anal?tico, onde os EEG foram avaliados independentemente por 2 examinadores sem pr?vio conhecimento do padr?o neurol?gico e da indica??o cl?nica. Ap?s an?lise visual do EEG, foram pesquisados os prontu?rios m?dicos de todas as crian?as inclu?das no estudo, a fim de definir e associar o padr?o neurol?gico com os par?metros fusos do sono, ondas agudas do v?rtex, e GFA. O padr?o neurol?gico foi classificado segundo a presen?a ou aus?ncia de comprometimento neurol?gico em padr?o neurol?gico normal (PNN) e padr?o neurol?gico anormal (PNA), respectivamente. Com base na an?lise visual dos EEG, foi caracterizado o GFA em duas categorias: 1) GFA presente (64,1%); 2) GFA ausente ( 35,9%); 3) FS normais (87,9%); 4) FS alterados (12,1%); 5) OAV normais (95,7%); 6) OAV alteradas (4,3%). A melhor express?o do GFA presente com PNN ocorreu nas faixas et?rias de 3 meses a 5 anos. Observou-se tamb?m que o GFA torna-se ausente a partir dos 10 anos de idade em crian?as com PNN. Comparando os 3 grafoelementos do sono, as OAV e FS, foram respectivamente predominantes nas crian?as com PNN. A an?lise estat?stica mostrou que existe uma forte associa??o de aus?ncia de GFA, como altera??o isolada, nos pacientes com PNA, uma vez que a raz?o de preval?ncia foi de 6,60. A associa??o torna-se mais forte, quando se considerou GFA ausente + FS alterados (RP=11,9) e GFA ausente + FS alterados + OAV alterados (RP= 6,68). O teste do qui-quadrado, com corre??o pela t?cnica de Yates, mostrou uma rela??o altamente significativa, quando envolvido o GFA. Assim, o GFA ausente foi mais expressivo no PNA que os FS e as OAV alterados. A associa??o se torna ainda mais forte a ponto de estabelecer uma rela??o com valor progn?stico, quando o GFA se encontra-se combinado com o FS. Embora estatisticamente significante, n?o houve associa??o quando as OAV se encontra isoladas em compara??o aos demais par?metros. Os dados obtidos neste estudo permitem afirmar que, entre os grafo- elementos do sono, o GFA, quando ausente nas faixas et?rias de 3 meses a 5 anos, ? um indicador de comprometimento neurol?gico, sendo tal conclus?o mais expressiva do que os par?metros FS e OAV. O GFA ? um par?metro idade dependente e deve ser valorizado e incorporado, sistematicamente, aos crit?rios de interpreta??o do tra?ado EEG do sono de crian?as, tanto no ponto de vista da avalia??o maturacional como dos dist?rbios neurol?gicos com comprometimento encef?lico

Background Creutzfeldt–Jakob disease is a rare and rapidly fatal neurodegenerative disease. Since clinicians may see only very few cases during their professional career, it is important to be familiar with the clinical presentation and progression, to perform appropriate investigations, and allow for quick diagnosis. Case presentation A 73-year-old British Caucasian woman presented with acute confusion of 2 weeks’ duration on a background of low mood following a recent bereavement. Her symptoms included behavioral change, visual hallucinations, vertigo, and recent falls. She was mildly confused, with left-sided hyperreflexia, a wide-based gait, and intention tremor in her left upper limb. Initial blood tests, computed tomography, and magnetic resonance imaging of her brain showed no significant abnormality. Following admission, she had rapid cognitive decline and developed florid and progressive neurological signs; a diagnosis of prion disease was suspected. A lumbar puncture was performed; cerebrospinal fluid was positive for 14–3-3 protein, real-time quaking-induced conversion, and raised levels of s-100b proteins were detected. An electroencephalogram showed bilateral periodic triphasic waves on a slow background. The diagnosis of probable Creutzfeldt–Jakob disease was made. Conclusions This case report highlights key features in the initial presentation and clinical development of a rare but invariably rapidly progressive and fatal disease. It emphasizes the importance of considering a unifying diagnosis for multifaceted clinical presentations. Although it is very rare, Creutzfeldt–Jakob disease should be considered a diagnosis for a mixed neuropsychiatric presentation, particularly with rapid progressive cognitive decline and development of neurological signs. However, to avoid overlooking early signal change on magnetic resonance imaging, it is important to take diffusion-weighted magnetic resonance imaging for all patients with neuropsychological symptoms. Importantly, early diagnosis also ensures the arrangement of suitable contamination control measures to minimize the risk of infection to health care professionals and other patients.

Les maladies à expansion de polyglutamine sont un ensemble de troubles neurodégénératives héréditaires se développant lorsqu’il y a répétitions de trinucléotides CAG dans les gènes causatifs au-delà d’un certain seuil. L’expansion des répétitions de trinucléotides CAG entraîne des désordres neurologiques héréditaires précoces, dont de multiples formes d’ataxie spinocérébelleuse (SCA). Parmi celles-ci, le type le plus commun et dominant est l’ataxie spinocérébelleuse de type 3 (SCA3), aussi connue sous le nom de la maladie de Machado-Joseph (MMJ). Ce dernier est un désordre neurologique progressif autosomique dominant. Le gène causatif de MMJ est ATXN3 (ATAXINE-3). Plusieurs études récentes suggèrent une association entre ce gène et la modulation du stress du réticulum endoplasmique (RE). Lors de ce travail de maîtrise, des souches transgéniques de C. elegans exprimant les formes sauvage et mutante du gène ATXN3 humain ont été générées. Les résultats suggèrent des phénotypes importants chez la souche transgénique mutante associés à la pathologie humaine: défaut de motilité, longévité réduite et profil neurodégénératif considérable. Ceci dit, ces résultats nous ont poussé à vouloir déterminer si l’utilisation des composés chimiques, connus en tant que modulateurs du stress du RE et possédant des rôles neuroprotecteurs, sont capables de restaurer les phénotypes notés. Les composés utilisés, c’est-à-dire le Bleu de Méthylène, le Salubrinal et le Guanabenz, ont démontré une capacité de corriger les phénotypes rapportés dans la souche transgénique mutante. De plus, ces composés ont aussi été en mesure de prévenir une augmentation du niveau du stress oxydatif et de la réponse au stress du RE exhibé chez les vers mutants. Par le développement de nouveaux modèles C. elegans pour la MMJ, où il y a expression du gène ATXN3 complet dans les motoneurones, il a été possible de trouver qu’une modulation chimique du stress du RE peut réduire considérablement la neurodégénérescence et par conséquent, être une possible nouvelle approche thérapeutique pour traiter cette pathologie. / Polyglutamine expansion diseases are a class of dominantly inherited neurodegenerative disorders that develop when a CAG repeat in the causative genes is unstably expanded above a certain threshold. The expansion of trinucleotide CAG repeats causes hereditary adult-onset neurodegenerative disorders such as multiple forms of spinocerebellar ataxia (SCA). The most common dominantly inherited spinocerebellar ataxia is the type 3 (SCA3) also known as Machado-Joseph disease (MJD), an autosomal dominant, progressive neurological disorder. The gene causing MJD is ATXN3 (ATAXIN-3): MJD is caused by an abnormal CAG trinucleotide repeat expansion in the ATXN3 gene. Several recent studies have shown that this gene is associated with endoplasmic reticulum (ER) stress. In this study, we generated transgenic C. elegans strains expressing wild type or mutant human ATXN3 genes and tested them for recovery of locomotor phenotype, lifespan and neurodegeneration phenotypes upon treatment with compounds known to modulate ER stress and having neuroprotective roles. We observed differences between both transgenic lines and found that the motility defects, the reduced lifespan and the neurodegeneration can be rescued by methylene blue, guanabenz and salubrinal. These compounds were also able to prevent the oxidative stress and the ER stress response induced by mutant transgenic worms. We introduce novel C. elegans models for MJD based on the expression of full-length ATXN3 in GABAergic motor neurons. Using these models we discovered that chemical modulation of the ER unfolded protein response reduced neurodegeneration and could be a new therapeutic approach for the treatment of MJD.