{"id":515,"date":"2025-10-28T19:58:53","date_gmt":"2025-10-28T10:58:53","guid":{"rendered":"https:\/\/neuroclub.jikei-neuroscience.com\/?p=515"},"modified":"2025-10-28T20:00:37","modified_gmt":"2025-10-28T11:00:37","slug":"2025-10-29","status":"publish","type":"post","link":"https:\/\/neuroclub.jikei-neuroscience.com\/?p=515","title":{"rendered":"2025-10-29"},"content":{"rendered":"\n

10\u670829\u65e5\u62c5\u5f53\u306e\u85ac\u7406\u5b66\u8b1b\u5ea7\u306e\u5ddd\u6751\u3067\u3059\u3002\u4ee5\u4e0b\u306epreprint\u306e\u8ad6\u6587\u3092\u7d39\u4ecb\u3044\u305f\u3057\u307e\u3059\u3002
A ketogenic diet mitigates hippocampal astrogliosis in epileptic brain<\/a>
Jae Hyouk Choi, Hugo J. Kim Shuhe Wang, Yueyang Cai, Ananya Achanta,
Srija Pamujula, Hamza M. Thange, Matthew Shtrahman, Jong M. Rho<\/p>\n\n\n\n

Abstract
<\/strong>The ketogenic diet (KD) is an established treatment for patients with
medically intractable epilepsy and is chiefly characterized by high
fat\/low-carbohydrate intake and the production of ketone bodies (KB)
such as \u03b2-hydroxybutyrate (BHB). However, after more than a century of
clinical use, the mechanisms underlying its efficacy remain unclear.
While prior investigations have examined the effects of the KD and its
metabolic substrates on synaptic transmission, few studies have explored
a potential connection between astrocytic ion channels and seizure
genesis. One essential function of astrocytes is spatial potassium
buffering which influences passive potassium conductance (PPC), and when
impaired, can result in neuronal hyperexcitability. In the present
study, we demonstrate that the KD can mitigate hippocampal astrogliosis
in the Kcna1-null (KO) mouse model of developmental epilepsy.
Specifically, we observed a significant increase in GFAP expression in
KO mice fed a control diet compared to wild-type (WT) mice, and that the
KD prevented this change. Furthermore, we noted a reduction in
hippocampal astrocytic PPC in epileptic mice, whereas KD-treated KO
animals exhibited nearly normal passive conductance levels. In this
regard, we found that while Kir4.1, TREK-1 and TWIK-1 RNA expression
levels were not significantly altered by KD treatment in either WT or KO
mice, BHB appeared to only minimally affect Kir4.1-mediated currents in
transfected HEK cells. Furthermore, bulk RNA-seq analysis of the various
treatment groups revealed KD-induced down-regulation of factors linked
to hippocampal astrogliosis. Our findings indicate that the KD protects
against epilepsy-associated astrogliosis and astrocytic PPC changes,
underscoring a novel mechanism of action, and implicate extracellular
potassium in its anti-seizure effects.<\/p>\n","protected":false},"excerpt":{"rendered":"

10\u670829\u65e5\u62c5\u5f53\u306e\u85ac\u7406\u5b66\u8b1b\u5ea7\u306e\u5ddd\u6751\u3067\u3059\u3002\u4ee5\u4e0b\u306epreprint\u306e\u8ad6\u6587\u3092\u7d39\u4ecb\u3044\u305f\u3057\u307e\u3059\u3002A ketogenic diet mitigates hippocampal astrogliosis in epileptic br…<\/p>\n","protected":false},"author":1,"featured_media":517,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_jetpack_memberships_contains_paid_content":false,"footnotes":""},"categories":[3],"tags":[],"class_list":["post-515","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-journal-club"],"jetpack_sharing_enabled":true,"jetpack_featured_media_url":"https:\/\/neuroclub.jikei-neuroscience.com\/wp-content\/uploads\/2025\/10\/image-3.png","_links":{"self":[{"href":"https:\/\/neuroclub.jikei-neuroscience.com\/index.php?rest_route=\/wp\/v2\/posts\/515","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/neuroclub.jikei-neuroscience.com\/index.php?rest_route=\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/neuroclub.jikei-neuroscience.com\/index.php?rest_route=\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/neuroclub.jikei-neuroscience.com\/index.php?rest_route=\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/neuroclub.jikei-neuroscience.com\/index.php?rest_route=%2Fwp%2Fv2%2Fcomments&post=515"}],"version-history":[{"count":1,"href":"https:\/\/neuroclub.jikei-neuroscience.com\/index.php?rest_route=\/wp\/v2\/posts\/515\/revisions"}],"predecessor-version":[{"id":516,"href":"https:\/\/neuroclub.jikei-neuroscience.com\/index.php?rest_route=\/wp\/v2\/posts\/515\/revisions\/516"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/neuroclub.jikei-neuroscience.com\/index.php?rest_route=\/wp\/v2\/media\/517"}],"wp:attachment":[{"href":"https:\/\/neuroclub.jikei-neuroscience.com\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=515"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/neuroclub.jikei-neuroscience.com\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=515"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/neuroclub.jikei-neuroscience.com\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=515"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}