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2018-07-10 - Colloque/Abstract - Anglais - 1 page(s)

Brunois Célestine , Ris Laurence , "Anti-GAD65 antibodies and their effects in the hippocampus - an in vivo model" in 11th FENS Forum of Neuroscience, Berlin, Germany, 2018

  • Codes CREF : Neurophysiologie (DI3224)
  • Unités de recherche UMONS : Neurosciences (M119)
  • Instituts UMONS : Institut des Sciences et Technologies de la Santé (Santé)
Texte intégral :

Abstract(s) :

(Anglais) Anti-GAD 65 antibodies are detected in patients suffering from various neurological pathologies including some with cognitive deficits. Because the hippocampus is a brain structure essential in cognition and memory, evaluate the effect of these antibodies in the hippocampus will bring some new insights in the understanding of these diseases. So my study tends to explore the impact of two anti-GAD65-specific antibodies in the hippocampus. For this purpose, a cannula is implanted into the third cerebral ventricle and connected to an osmotic pump. First, the antibodies diffusion into the brain was characterized thanks to a fluorescent labeling. Second, electrophysiological measures were performed in acute hippocampal slice to study long-term potentiation of synaptic response in the Ammon’s horn. The results showed a significant decrease of LTP in mice treated with b78 antibodies compared to groups treated with b96.11 or saline. Third, immuno-histological methods targeting astrocytes and activated microgliocytes revealed an activation of these immune cells in mice treated with b78. Others specific procedures indicated an increase of the number of proliferating cells in the hippocampus of these mice. This structure seems to be intact but revealed an infiltration of immune cells in periphery of ventricles and blood vessels. Furthermore, cognitive impairment was studied by a behavioral test: the contextual fear conditioning. It showed a decrease of both basal movement and freezing in b78 mice. So, our results suggest that anti-GAD65 b78 antibodies have multiple effects in the hippocampus. The specificity of these effects will be further assessed by using GAD65 knock-out mice.

(Anglais) Anti-GAD 65 antibodies are detected in patients suffering from various neurological pathologies including some with cognitive deficits. Because the hippocampus is a brain structure essential in cognition and memory, evaluate the effect of these antibodies in the hippocampus will bring some new insights in the understanding of these diseases. So my study tends to explore the impact of two anti-GAD65-specific antibodies in the hippocampus. For this purpose, a cannula is implanted into the third cerebral ventricle and connected to an osmotic pump. First, the antibodies diffusion into the brain was characterized thanks to a fluorescent labeling. Second, electrophysiological measures were performed in acute hippocampal slice to study long-term potentiation of synaptic response in the Ammon’s horn. The results showed a significant decrease of LTP in mice treated with b78 antibodies compared to groups treated with b96.11 or saline. Third, immuno-histological methods targeting astrocytes and activated microgliocytes revealed an activation of these immune cells in mice treated with b78. Others specific procedures indicated an increase of the number of proliferating cells in the hippocampus of these mice. This structure seems to be intact but revealed an infiltration of immune cells in periphery of ventricles and blood vessels. Furthermore, cognitive impairment was studied by a behavioral test: the contextual fear conditioning. It showed a decrease of both basal movement and freezing in b78 mice. So, our results suggest that anti-GAD65 b78 antibodies have multiple effects in the hippocampus. The specificity of these effects will be further assessed by using GAD65 knock-out mice.

(Anglais) Anti-GAD 65 antibodies are detected in patients suffering from various neurological pathologies including some with cognitive deficits. Because the hippocampus is a brain structure essential in cognition and memory, evaluate the effect of these antibodies in the hippocampus will bring some new insights in the understanding of these diseases. So my study tends to explore the impact of two anti-GAD65-specific antibodies in the hippocampus. For this purpose, a cannula is implanted into the third cerebral ventricle and connected to an osmotic pump. First, the antibodies diffusion into the brain was characterized thanks to a fluorescent labeling. Second, electrophysiological measures were performed in acute hippocampal slice to study long-term potentiation of synaptic response in the Ammon’s horn. The results showed a significant decrease of LTP in mice treated with b78 antibodies compared to groups treated with b96.11 or saline. Third, immuno-histological methods targeting astrocytes and activated microgliocytes revealed an activation of these immune cells in mice treated with b78. Others specific procedures indicated an increase of the number of proliferating cells in the hippocampus of these mice. This structure seems to be intact but revealed an infiltration of immune cells in periphery of ventricles and blood vessels. Furthermore, cognitive impairment was studied by a behavioral test: the contextual fear conditioning. It showed a decrease of both basal movement and freezing in b78 mice. So, our results suggest that anti-GAD65 b78 antibodies have multiple effects in the hippocampus. The specificity of these effects will be further assessed by using GAD65 knock-out mice.