The Experts below are selected from a list of 3840 Experts worldwide ranked by ideXlab platform
Albert R La Spada - One of the best experts on this subject based on the ideXlab platform.
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Autophagy activation and enhanced mitophagy characterize the Purkinje cells of pcd mice prior to neuronal death
Molecular Brain, 2009Co-Authors: Lisa Chakrabarti, Jeremiah Eng, Nishi Ivanov, Gwenn A Garden, Albert R La SpadaAbstract:Purkinje cells are a class of specialized neurons in the Cerebellum, and are among the most metabolically active of all neurons, as they receive immense synaptic stimulation, and provide the only efferent output from the Cerebellum. Degeneration of Purkinje cells is a common feature of inherited ataxias in humans and mice. To understand Purkinje neuron Degeneration, investigators have turned to naturally occurring Purkinje cell Degeneration phenotypes in mice to identify key regulatory proteins and cellular pathways. The Purkinje cell Degeneration ( pcd ) mouse is a recessive mutant characterized by complete and dramatic post-natal, cell autonomous Purkinje neuron Degeneration and death. As the basis of Purkinje cell death in pcd is unresolved, and contradictory data has emerged for the role of autophagy in Purkinje cell Degeneration, we studied the mechanism of Purkinje cell death in pcd mice. BAX null status did not suppress Purkinje neuron death in pcd mice, indicating that classic apoptosis is not responsible for Purkinje cell loss. Interestingly, LC3 Western blot analysis and GFP-LC3 immunostaining of degenerating pcd Cerebellum revealed activation of the autophagy pathway. Ultrastructural studies confirmed increased autophagy pathway activity in Purkinje cells, and yielded evidence for mitophagy, in agreement with LC3 immunoblotting of cerebellar fractions. As p62 levels were decreased in pcd Cerebellum, our findings suggest that pcd Purkinje cell neurons can execute effective autophagy. However, our results support a role for dysregulated autophagy activation in pcd , and suggest that increased or aberrant mitophagy contributes to the Purkinje cell Degeneration in pcd mice.
M. Didier-bazes - One of the best experts on this subject based on the ideXlab platform.
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Serotoninergic control of the activity and expression of glial GABA transporters in the rat Cerebellum
Glia, 1998Co-Authors: Brigitte Voutsinos, Magali Dutuit, Ariel Reboul, Michelle Fèvre-montange, Arlette Bernard, Paul Trouillas, Hideo Akaoka, Marie-françoise Belin, M. Didier-bazesAbstract:Gamma-Aminobutyric acid (GABA) transporters (GAT-1, GAT-2, and GAT-3) play a key role in the termination of GABA transmission and the regulation of extracellular GABA concentrations. In the present study, pharmacological, cellular, and molecular analyses provide evidence for a modulatory effect of serotoninergic neurons on the activity and expression of glial GABA transporters in the rat Cerebellum. Degeneration of serotoninergic neurons after in vivo 5,7-dihydroxytryptamine (5,7-DHT) treatment resulted in a significant decrease (-27%) in [3H]-GABA uptake into cerebellar punches. This decrease probably occurred via inhibition of GAT-2 or GAT-3 activity since their inhibitor, beta-alanine, induced a decrease in [3H]-GABA uptake in punches of sham-operated rats (-28%), but not in punches of 5,7-DHT-treated rats, demonstrating that serotonin terminal Degeneration had already impaired the beta-alanine-sensitive component of GABA uptake. In contrast, nipecotic acid, a preferential inhibitor of GAT-1, induced comparable decreases in [3H]-GABA uptake comparable in punches of 5,7-DHT (-38%) versus sham-operated rats (-37%). The decreases in GAT-1 (-16%), GAT-2 (-34%), and GAT-3 (-32%) mRNA levels after 5,7-DHT treatment (detected by quantitative RT-PCR) are consistent with a serotoninergic control of GABA transporter expression at the transcriptional level. The cellular distribution of GAT-2 and GAT-3 mRNA, shown by in situ hybridization, suggests a glial localization of these transporters in the Cerebellum and demonstrated a preferential anatomical localization of GAT-2 mRNA in the granular layer and of GAT-3 mRNA in the deep cerebellar nuclei. A direct serotoninergic control of glial GABA uptake was further demonstrated in vitro since serotonin stimulated the activity and mRNA expression of the GABA transporters in cerebellar astrocyte cultures.
Je Kyung Seong - One of the best experts on this subject based on the ideXlab platform.
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Neuronal differentiation and developmental characteristics in the dentate gyrus of staggerer mutant mice.
BMB reports, 2010Co-Authors: In Koo Hwang, Jae Hoon Shin, Sung Hee Baek, Yeo Sung Yoon, Je Kyung SeongAbstract:Homozygous staggerer (RORa(sg/sg)) mice showed a severe ataxia caused by Cerebellum Degeneration. Decreased and dysfunctional Rora is a main cause of this neurologic phenotype. The phenotype of staggerer mice has been well known in Cerebellum. However, there has been rarely reported about cerebrum even though of staggerer is expressed in merely Cerebellum but hippocampus, thalamus, cortex, and olfactory bulb. The expressions of Ki67, doublecortin (DCX), and NeuN, which are cell proliferation, neuronal differentiation and mature neuron markers, respectively, were measured with immunohistochemistry in dentate gyrus in staggerer mice in order to uncover whether staggerer can affect the change in dentate gyrus. The immunoreactivities of DCX and NeuN were significantly reduced in the dentate gyrus of staggerer mice than normal control, while Ki67 were rarely unchanged in staggerer mice. These results suggest that staggerer mutation has an influence on the neuronal differentiation and development not only in Cerebellum but also in dentate gyrus.
P.n. Cooper - One of the best experts on this subject based on the ideXlab platform.
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Pulmonary lymphoma in a patient with coeliac disease presenting with paraneoplastic cerebellar Degeneration
Respiratory Medicine Extra, 2005Co-Authors: D.g. Fullerton, R. Chisholm, H. Reid, R. O’driscoll, P.n. CooperAbstract:Summary Objective and importance Neurological complications of coeliac disease are well recognized (e.g. gluten taxia) and T cell lymphoma is an associated complication of this disease. However, pulmonary lymphoma and an associated paraneoplastic phenomenon in a patient with coeliac disease has not been previously reported. There are no previous case reports of pulmonary lymphoma presenting with opthalmoplegia—a paraneoplastic phenomenon. Clinical presentation Fifty-five-year-old man presented with diplopia. He had a history of coeliac disease and developed an aggressive T cell pulmonary lymphoma, diagnosed at autopsy. Examination of his Cerebellum showed Purkinje cell loss consistent with paraneoplastic Cerebellum Degeneration. Intervention Delay in diagnosis of this condition meant that intervention was not possible. Conclusion This case demonstrates that diagnosis is difficult but that the possibility should be bourne in mind before attributing cerebellar dysfunction to other pathologies.
Lisa Chakrabarti - One of the best experts on this subject based on the ideXlab platform.
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Autophagy activation and enhanced mitophagy characterize the Purkinje cells of pcd mice prior to neuronal death
Molecular Brain, 2009Co-Authors: Lisa Chakrabarti, Jeremiah Eng, Nishi Ivanov, Gwenn A Garden, Albert R La SpadaAbstract:Purkinje cells are a class of specialized neurons in the Cerebellum, and are among the most metabolically active of all neurons, as they receive immense synaptic stimulation, and provide the only efferent output from the Cerebellum. Degeneration of Purkinje cells is a common feature of inherited ataxias in humans and mice. To understand Purkinje neuron Degeneration, investigators have turned to naturally occurring Purkinje cell Degeneration phenotypes in mice to identify key regulatory proteins and cellular pathways. The Purkinje cell Degeneration ( pcd ) mouse is a recessive mutant characterized by complete and dramatic post-natal, cell autonomous Purkinje neuron Degeneration and death. As the basis of Purkinje cell death in pcd is unresolved, and contradictory data has emerged for the role of autophagy in Purkinje cell Degeneration, we studied the mechanism of Purkinje cell death in pcd mice. BAX null status did not suppress Purkinje neuron death in pcd mice, indicating that classic apoptosis is not responsible for Purkinje cell loss. Interestingly, LC3 Western blot analysis and GFP-LC3 immunostaining of degenerating pcd Cerebellum revealed activation of the autophagy pathway. Ultrastructural studies confirmed increased autophagy pathway activity in Purkinje cells, and yielded evidence for mitophagy, in agreement with LC3 immunoblotting of cerebellar fractions. As p62 levels were decreased in pcd Cerebellum, our findings suggest that pcd Purkinje cell neurons can execute effective autophagy. However, our results support a role for dysregulated autophagy activation in pcd , and suggest that increased or aberrant mitophagy contributes to the Purkinje cell Degeneration in pcd mice.