{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T02:52:39Z","timestamp":1760237559624,"version":"build-2065373602"},"reference-count":105,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2020,6,3]],"date-time":"2020-06-03T00:00:00Z","timestamp":1591142400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000781","name":"European Research Council","doi-asserted-by":"publisher","award":["321501"],"award-info":[{"award-number":["321501"]}],"id":[{"id":"10.13039\/501100000781","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003977","name":"Israel Science Foundation","doi-asserted-by":"publisher","award":["1016\/18"],"award-info":[{"award-number":["1016\/18"]}],"id":[{"id":"10.13039\/501100003977","id-type":"DOI","asserted-by":"publisher"}]},{"name":"NOFAR Israel Innovations Authority","award":["65812"],"award-info":[{"award-number":["65812"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Stereotypic behavior (SB) is common in emotional stress-involved psychiatric disorders and is often attributed to glutamatergic impairments, but the underlying molecular mechanisms are unknown. Given the neuro-modulatory role of acetylcholine, we sought behavioral-transcriptomic links in SB using TgR transgenic mice with impaired cholinergic transmission due to over-expression of the stress-inducible soluble \u2018readthrough\u2019 acetylcholinesterase-R splice variant AChE-R. TgR mice showed impaired organization of behavior, performance errors in a serial maze test, escape-like locomotion, intensified reaction to pilocarpine and reduced rearing in unfamiliar situations. Small-RNA sequencing revealed 36 differentially expressed (DE) microRNAs in TgR mice hippocampi, 8 of which target more than 5 cholinergic transcripts. Moreover, compared to FVB\/N mice, TgR prefrontal cortices displayed individually variable changes in over 400 DE mRNA transcripts, primarily acetylcholine and glutamate-related. Furthermore, TgR brains presented c-fos over-expression in motor behavior-regulating brain regions and immune-labeled AChE-R excess in the basal ganglia, limbic brain nuclei and the brain stem, indicating a link with the observed behavioral phenotypes. Our findings demonstrate association of stress-induced SB to previously unknown microRNA-mediated perturbations of cholinergic\/glutamatergic networks and underscore new therapeutic strategies for correcting stereotypic behaviors.<\/jats:p>","DOI":"10.3390\/biom10060848","type":"journal-article","created":{"date-parts":[[2020,6,4]],"date-time":"2020-06-04T04:36:09Z","timestamp":1591245369000},"page":"848","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Cholinergic Stress Signals Accompany MicroRNA-Associated Stereotypic Behavior and Glutamatergic Neuromodulation in the Prefrontal Cortex"],"prefix":"10.3390","volume":"10","author":[{"given":"Gilli","family":"Moshitzky","sequence":"first","affiliation":[{"name":"The Institute of Life Sciences and The Edmond and Lily Safra Center of Brain Science, The Hebrew University of Jerusalem, Jerusalem 9190401, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shai","family":"Shoham","sequence":"additional","affiliation":[{"name":"Herzog Medical Center, Givat Shaul, P.O. Box 3900, Jerusalem 9103702, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8467-5085","authenticated-orcid":false,"given":"Nimrod","family":"Madrer","sequence":"additional","affiliation":[{"name":"The Institute of Life Sciences and The Edmond and Lily Safra Center of Brain Science, The Hebrew University of Jerusalem, Jerusalem 9190401, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amir Mouhammed","family":"Husain","sequence":"additional","affiliation":[{"name":"The Institute of Life Sciences and The Edmond and Lily Safra Center of Brain Science, The Hebrew University of Jerusalem, Jerusalem 9190401, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David S.","family":"Greenberg","sequence":"additional","affiliation":[{"name":"The Institute of Life Sciences and The Edmond and Lily Safra Center of Brain Science, The Hebrew University of Jerusalem, Jerusalem 9190401, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Raz","family":"Yirmiya","sequence":"additional","affiliation":[{"name":"Department of Psychology, The Hebrew University of Jerusalem, Jerusalem 9190401, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoram","family":"Ben-Shaul","sequence":"additional","affiliation":[{"name":"Department of Medical Neurobiology, The Institute of Medical Research Israel-Canada, Jerusalem 9112102, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0955-526X","authenticated-orcid":false,"given":"Hermona","family":"Soreq","sequence":"additional","affiliation":[{"name":"The Institute of Life Sciences and The Edmond and Lily Safra Center of Brain Science, The Hebrew University of Jerusalem, Jerusalem 9190401, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,6,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1002\/mds.870120109","article-title":"The characterization and outcome of stereotypical movements in nonautistic children","volume":"12","author":"Tan","year":"1997","journal-title":"Mov. 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