Alzheimer's disease risk gene BIN1 induces Tau-dependent network hyperexcitability — MEA Axion Biosciences Maestro Recordings, Figure 6
| العنوان: | Alzheimer's disease risk gene BIN1 induces Tau-dependent network hyperexcitability — MEA Axion Biosciences Maestro Recordings, Figure 6 |
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| المؤلفون: | Voskobiynyk, Yuliya, Roth, Jonathan, Cochran, J Nicholas, Rush, Travis, Carullo, Nancy, Mesina, Jacob, Waqas, Mohhamad, Vollmer, Rachael, Day, Jeremy, McMahon, Lori, Roberson, Erik |
| سنة النشر: | 2020 |
| المجموعة: | Zenodo |
| الوصف: | Genome-wide association studies identified the BIN1 locus as a leading modulator of genetic risk in Alzheimer's disease (AD). One limitation in understanding BIN1's contribution to AD is its unknown function in the brain. AD-associated BIN1 variants are generally noncoding and likely change expression. Here, we determined the effects of increasing expression of the major neuronal isoform of human BIN1 in cultured rat hippocampal neurons. Higher BIN1 induced network hyperexcitability on multielectrode arrays, increased frequency of synaptic transmission, and elevated calcium transients, indicating that increasing BIN1 drives greater neuronal activity. In exploring the mechanism of these effects on neuronal physiology, we found that BIN1 interacted with L-type voltage-gated calcium channels (LVGCCs) and that BIN1–LVGCC interactions were modulated by Tau in rat hippocampal neurons and mouse brain. Finally, Tau reduction prevented BIN1-induced network hyperexcitability. These data shed light on BIN1's neuronal function and suggest that it may contribute to Tau-dependent hyperexcitability in AD. ; An excel file with the plate layout is uploaded. Funding provided by: National Institutes of HealthCrossref Funder Registry ID: http://dx.doi.org/10.13039/100000002AwardTest Number: RF1AG059405Funding provided by: Alzheimer's AssociationCrossref Funder Registry ID: http://dx.doi.org/10.13039/100000957FundingTest provided by: Weston Brain InstituteCrossref Funder Registry ID: http://dx.doi.org/10.13039/100012479Test ; Multi electrode array cultures For 6-well multielectrode array recordings, neurons were plated at 100,000 per well in six-well MEA plates (ALA Scientific, ALAMEA-MEMMR5). For 48-well plate multielectrode array recordings, neurons were plated at 30,000 per well in 48-well MEA plates (Axion Biosystems, M768-tMEA-48B-5). BIN1 constructs and vectors A BIN1-mKate2 (GE Dharmacon, OHS5894-202501160) construct was developed to encode human BIN1 isoform 1 (593 AA, the major neuronal isoform) tagged with mKate2 (Evrogen, FP184, to ... |
| نوع الوثيقة: | dataset |
| اللغة: | unknown |
| العلاقة: | https://zenodo.org/communities/dryadTest; https://zenodo.org/record/3998336Test; https://doi.org/10.5061/dryad.rbnzs7h8zTest; oai:zenodo.org:3998336 |
| DOI: | 10.5061/dryad.rbnzs7h8z |
| الإتاحة: | https://doi.org/10.5061/dryad.rbnzs7h8zTest https://doi.org/10.7554/eLife.57354Test https://zenodo.org/record/3998336Test |
| حقوق: | info:eu-repo/semantics/openAccess ; https://creativecommons.org/publicdomain/zero/1.0/legalcodeTest |
| رقم الانضمام: | edsbas.6EFF4971 |
| قاعدة البيانات: | BASE |
| DOI: | 10.5061/dryad.rbnzs7h8z |
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