{"id":162246,"date":"2023-04-15T16:26:57","date_gmt":"2023-04-15T21:26:57","guid":{"rendered":"https:\/\/lifeboat.com\/blog\/2023\/04\/inhibition-of-rho-kinase-ameliorates-decreased-spine-density-in-the-medial-prefrontal-cortex-and-methamphetamine-induced-cognitive-dysfunction-in-mice-carrying-schizophrenia-associated-mutations-of-th"},"modified":"2023-04-15T16:26:57","modified_gmt":"2023-04-15T21:26:57","slug":"inhibition-of-rho-kinase-ameliorates-decreased-spine-density-in-the-medial-prefrontal-cortex-and-methamphetamine-induced-cognitive-dysfunction-in-mice-carrying-schizophrenia-associated-mutations-of-th","status":"publish","type":"post","link":"https:\/\/lifeboat.com\/blog\/2023\/04\/inhibition-of-rho-kinase-ameliorates-decreased-spine-density-in-the-medial-prefrontal-cortex-and-methamphetamine-induced-cognitive-dysfunction-in-mice-carrying-schizophrenia-associated-mutations-of-th","title":{"rendered":"Inhibition of Rho-kinase ameliorates decreased spine density in the medial prefrontal cortex and methamphetamine-induced cognitive dysfunction in mice carrying schizophrenia-associated mutations of the Arhgap10 gene"},"content":{"rendered":"<p><a class=\"blog-photo\" href=\"https:\/\/lifeboat.com\/blog.images\/inhibition-of-rho-kinase-ameliorates-decreased-spine-density-in-the-medial-prefrontal-cortex-and-methamphetamine-induced-cognitive-dysfunction-in-mice-carrying-schizophrenia-associated-mutations-of-th.jpg\"><\/a><\/p>\n<p>Reversing schizophrenia with gene therapy year 2023.<\/p>\n<hr>\n<p>Copy-number variations in the <em>ARHGAP10<\/em> gene encoding Rho GTPase\u2013activating protein 10 are associated with schizophrenia. Model mice (<em>Arhgap10<\/em> S490P\/NHEJ mice) that carry \u201cdouble-hit\u201d mutations in the <em>Arhgap10<\/em> gene mimic the schizophrenia in a Japanese patient, exhibiting altered spine density, methamphetamine-induced <a href=\"https:\/\/www.sciencedirect.com\/topics\/pharmacology-toxicology-and-pharmaceutical-science\/cognitive-defect\" title=\"Learn more about cognitive dysfunction from ScienceDirect's AI-generated Topic Pages\" class=\"\">cognitive dysfunction<\/a>, and activation of RhoA\/Rho-kinase signaling. However, it remains unclear whether the activation of RhoA\/Rho-kinase signaling due to schizophrenia-associated <em>Arhgap10<\/em> mutations causes the phenotypes of these model mice. Here, we investigated the effects of <a href=\"https:\/\/www.sciencedirect.com\/topics\/pharmacology-toxicology-and-pharmaceutical-science\/fasudil\" title=\"Learn more about fasudil from ScienceDirect's AI-generated Topic Pages\" class=\"\">fasudil<\/a>, a brain permeable Rho-kinase inhibitor, on altered spine density in the medial prefrontal cortex (mPFC) and on methamphetamine-induced cognitive impairment in a touchscreen\u2011based visual discrimination task in <em>Arhgap10<\/em> S490P\/NHEJ mice. Fasudil (20 mg\/kg, intraperitoneal) suppressed the increased phosphorylation of myosin phosphatase\u2013targeting subunit 1, a substrate of Rho-kinase, in the striatum and mPFC of <em>Arhgap10<\/em> S490P\/NHEJ mice. In addition, daily oral administration of fasudil (20 mg\/kg\/day) for 7 days ameliorated the reduced spine density of layer 2\/3 pyramidal neurons in the mPFC. Moreover, fasudil (3\u201320 mg\/kg, intraperitoneal) rescued the methamphetamine (0.3 mg\/kg)-induced cognitive impairment of visual discrimination in <em>Arhgap10<\/em> S490P\/NHEJ mice. Our results suggest that Rho-kinase plays significant roles in the neuropathological changes in spine morphology and in the vulnerability of cognition to methamphetamine in mice with schizophrenia-associated <em>Arhgap10<\/em> mutations.<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Reversing schizophrenia with gene therapy year 2023. Copy-number variations in the ARHGAP10 gene encoding Rho GTPase\u2013activating protein 10 are associated with schizophrenia. Model mice (Arhgap10 S490P\/NHEJ mice) that carry \u201cdouble-hit\u201d mutations in the Arhgap10 gene mimic the schizophrenia in a Japanese patient, exhibiting altered spine density, methamphetamine-induced cognitive dysfunction, and activation of RhoA\/Rho-kinase signaling. However, [\u2026]<\/p>\n","protected":false},"author":513,"featured_media":0,"comment_status":"open","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[11,412,47],"tags":[],"class_list":["post-162246","post","type-post","status-publish","format-standard","hentry","category-biotech-medical","category-genetics","category-neuroscience"],"_links":{"self":[{"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/posts\/162246","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/users\/513"}],"replies":[{"embeddable":true,"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/comments?post=162246"}],"version-history":[{"count":0,"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/posts\/162246\/revisions"}],"wp:attachment":[{"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/media?parent=162246"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/categories?post=162246"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/tags?post=162246"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}