P1‐129: CELL‐AUTONOMOUS AND EFFECTS OF NEURONAL BIN1 LOSS IN VIVO Article Swipe

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Hameetha Banu Rajamohamed Sait , Kathleen M. McAvoy , Galina Marsh , Michael Peterson , Taylor L. Reynolds , Jake Gagnon , Sarah Geisler , Chris Roberts , Richard M. Ransohoff , Andrea Crotti ·

YOU? · · 2019 · Open Access · · DOI: https://doi.org/10.1016/j.jalz.2019.06.684

BIN1 has been identified as the most important risk locus for Late Onset Alzheimer's Disease (LOAD), after ApoE. BIN1-associated SNPs correlate with tau deposition as well as with hippocampal atrophy. Furthermore, while the total amount of BIN1 mRNA increases, the level of neuronal-specific BIN1 isoform 1 protein is decreased in sporadic AD cases and this decrease parallels to neuronal loss. In this study, we knocked-down endogenous Bin1 either in the hippocampus or conditionally in neurons of mice expressing tau P301S (PS19) to understand whether the loss of BIN1 in conjunction to tau deposition is causative of neuronal loss. We delivered Bin1-shRNA into the hippocampus of PS19 mice via stereotaxic injection of Adeno-associated Virus (AAV)-Bin1 shRNA. To investigate whether the neuronal loss is due to deletion of Bin1 in neurons in presence or in absence of tau P301S, we bred Bin1fl/fl mice with mice expressing Cre under the neuronal promoter of Thy1, and subsequently with PS19. We observed a statistically significant reduction in the number of neurons in the hippocampus of mice injected with AAV-Bin1 shRNA in comparison with mice injected with AAV control. We observed that mice lacking Bin1 exclusively in neurons and expressing tau P301S die earlier, but they don't show any difference in the number of neurons. The loss of neuronal Bin1 resulted in an increased susceptibility to pharmacologically-induced seizure, and an increased activation of c-fos in vivo. Taken together, our data suggest that the effect of BIN1 on Alzheimer's Disease risk could be partially due to a cell autonomous role of neuronal Bin1, eventually exacerbated by the presence of mutant tau. Further studies are currently ongoing to understand the mechanisms underlying these effects.

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Hippocampal formation In vivo Hippocampus Biology Neurodegeneration Small hairpin RNA Neuroscience Molecular biology Endocrinology Internal medicine Gene knockdown Medicine Cell culture Genetics Disease

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Type: article
Language: en
Landing Page: https://doi.org/10.1016/j.jalz.2019.06.684
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DOI: https://doi.org/10.1016/j.jalz.2019.06.684

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Title: P1‐129: CELL‐AUTONOMOUS AND EFFECTS OF NEURONAL BIN1 LOSS IN VIVO

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Language: en

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Publication year: 2019

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Publication date: 2019-07-01

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Authors: Hameetha Banu Rajamohamed Sait, Kathleen M. McAvoy, Galina Marsh, Michael Peterson, Taylor L. Reynolds, Jake Gagnon, Sarah Geisler, Chris Roberts, Richard M. Ransohoff, Andrea Crotti

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Landing page: https://doi.org/10.1016/j.jalz.2019.06.684

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Concepts: Hippocampal formation, In vivo, Hippocampus, Biology, Neurodegeneration, Small hairpin RNA, Neuroscience, Molecular biology, Endocrinology, Internal medicine, Gene knockdown, Medicine, Cell culture, Genetics, Disease

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