{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:21:47Z","timestamp":1760145707941,"version":"build-2065373602"},"reference-count":69,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2024,8,20]],"date-time":"2024-08-20T00:00:00Z","timestamp":1724112000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000268","name":"BBSRC","doi-asserted-by":"publisher","award":["BB\/L021382\/1","ISSF-2019","INCS-2019-225"],"award-info":[{"award-number":["BB\/L021382\/1","ISSF-2019","INCS-2019-225"]}],"id":[{"id":"10.13039\/501100000268","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Institutional Strategic Support Fund, the University of Oxford","award":["BB\/L021382\/1","ISSF-2019","INCS-2019-225"],"award-info":[{"award-number":["BB\/L021382\/1","ISSF-2019","INCS-2019-225"]}]},{"name":"Commonwealth Scholarship","award":["BB\/L021382\/1","ISSF-2019","INCS-2019-225"],"award-info":[{"award-number":["BB\/L021382\/1","ISSF-2019","INCS-2019-225"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biology"],"abstract":"<jats:p>In ataxia disorders, motor incoordination (ataxia) is primarily linked to the dysfunction and degeneration of cerebellar Purkinje cells (PCs). In spinocerebellar ataxia 6 (SCA6), for example, decreased BDNF\u2013TrkB signalling appears to contribute to PC dysfunction and ataxia. However, abnormal BDNF\u2013TrkB signalling in granule cells (GCs) may contribute to PC dysfunction and incoordination in ataxia disorders, as TrkB receptors are also present in GCs that provide extensive input to PCs. This study investigated whether dysfunctional BDNF\u2013TrkB signalling restricted to a specific subset of cerebellar GCs can generate ataxia in mice. To address this question, our research focused on TrkbPenk-KO mice, in which the TrkB receptor was removed from enkephalinergic precursor-derived cerebellar GCs. We found that deleting Ntrk2, encoding the TrkB receptor, eventually interfered with PC function, leading to ataxia symptoms in the TrkbPenk-KO mice without affecting their cerebellar morphology or levels of selected synaptic markers. These findings suggest that dysfunctional BDNF\u2013TrkB signalling in a subset of cerebellar GCs alone is sufficient to trigger ataxia symptoms and may contribute to motor incoordination in disorders like SCA6.<\/jats:p>","DOI":"10.3390\/biology13080637","type":"journal-article","created":{"date-parts":[[2024,8,20]],"date-time":"2024-08-20T06:07:35Z","timestamp":1724134055000},"page":"637","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Ablation of TrkB from Enkephalinergic Precursor-Derived Cerebellar Granule Cells Generates Ataxia"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9179-2194","authenticated-orcid":false,"given":"Elena","family":"Eliseeva","sequence":"first","affiliation":[{"name":"Department of Pharmacology, University of Oxford, Oxford OX1 3QT, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohd Yaseen","family":"Malik","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, University of Oxford, Oxford OX1 3QT, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4246-4765","authenticated-orcid":false,"given":"Liliana","family":"Minichiello","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, University of Oxford, Oxford OX1 3QT, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,8,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"672","DOI":"10.1093\/ptj\/77.6.672","article-title":"Mechanisms of Ataxia","volume":"77","author":"Bastian","year":"1997","journal-title":"Phys. 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