{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T11:55:17Z","timestamp":1785758117518,"version":"3.56.0"},"reference-count":108,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2023,6,14]],"date-time":"2023-06-14T00:00:00Z","timestamp":1686700800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Neuroscience Research"],"published-print":{"date-parts":[[2023,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Aging is associated with cognitive decline and is the main risk factor for a myriad of conditions including neurodegeneration and stroke. Concomitant with aging is the progressive accumulation of misfolded proteins and loss of proteostasis. Accumulation of misfolded proteins in the endoplasmic reticulum (ER) leads to ER stress and activation of the unfolded protein response (UPR). The UPR is mediated, in part, by the eukaryotic initiation factor 2\u03b1 (eIF2\u03b1) kinase protein kinase R\u2010like ER kinase (PERK). Phosphorylation of eIF2\u03b1 reduces protein translation as an adaptive mechanism but this also opposes synaptic plasticity. PERK, and other eIF2\u03b1 kinases, have been widely studied in neurons where they modulate both cognitive function and response to injury. The impact of astrocytic PERK signaling in cognitive processes was previously unknown. To examine this, we deleted PERK from astrocytes (AstroPERK\n                    <jats:sup>KO<\/jats:sup>\n                    ) and examined the impact on cognitive functions in middle\u2010aged and old mice of both sexes. Additionally, we tested the outcome following experimental stroke using the transient middle cerebral artery occlusion (MCAO) model. Tests of short\u2010term and long\u2010term learning and memory as well as of cognitive flexibility in middle\u2010aged and old mice revealed that astrocytic PERK does not regulate these processes. Following MCAO, AstroPERK\n                    <jats:sup>KO<\/jats:sup>\n                    had increased morbidity and mortality. Collectively, our data demonstrate that astrocytic PERK has limited impact on cognitive function and has a more prominent role in the response to neural injury.\n                  <\/jats:p>","DOI":"10.1002\/jnr.25224","type":"journal-article","created":{"date-parts":[[2023,6,14]],"date-time":"2023-06-14T06:53:05Z","timestamp":1686725585000},"page":"1586-1610","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Astrocytic deletion of protein kinase R\u2010like\n                    <scp>ER<\/scp>\n                    kinase (\n                    <scp>PERK<\/scp>\n                    ) does not affect learning and memory in aged mice but worsens outcome from experimental stroke"],"prefix":"10.1002","volume":"101","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8798-5484","authenticated-orcid":false,"given":"Anirudhya","family":"Lahiri","sequence":"first","affiliation":[{"name":"Department of Microbiology, Immunology and Cell Biology West Virginia University  Morgantown West Virginia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James C.","family":"Walton","sequence":"additional","affiliation":[{"name":"Department of Neuroscience West Virginia University  Morgantown West Virginia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ning","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Neuroscience West Virginia University  Morgantown West Virginia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neil","family":"Billington","sequence":"additional","affiliation":[{"name":"Department of Biochemistry West Virginia University  Morgantown West Virginia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. Courtney","family":"DeVries","sequence":"additional","affiliation":[{"name":"Department of Neuroscience West Virginia University  Morgantown West Virginia USA"},{"name":"Rockefeller Neuroscience Institute West Virginia University  Morgantown West Virginia USA"},{"name":"Department of Medicine, Division of Hematology and Oncology West Virginia University  Morgantown West Virginia USA"},{"name":"WVU Cancer Institute  Morgantown West Virginia USA"},{"name":"West Virginia Clinical and Translational Science Institute West Virginia University  Morgantown West Virginia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gordon P.","family":"Meares","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology and Cell Biology West Virginia University  Morgantown West Virginia USA"},{"name":"Department of Neuroscience West Virginia University  Morgantown West Virginia USA"},{"name":"Rockefeller Neuroscience Institute West Virginia University  Morgantown West Virginia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,6,14]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2017.05.033"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.2001.00462.x"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddx370"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2016.06.027"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2010.11.007"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIR.0000000000000659"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-biochem-062209-093836"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2014.09.042"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-013-1490-2"},{"key":"e_1_2_11_11_1","doi-asserted-by":"crossref","unstructured":"Cabral\u2010Miranda F. 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