{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T11:22:52Z","timestamp":1785410572409,"version":"3.56.0"},"posted":{"date-parts":[[2025,11,29]]},"group-title":"Neuroscience","reference-count":46,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,11,29]],"date-time":"2025-11-29T00:00:00Z","timestamp":1764374400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"NIH","award":["R35GM142726"],"award-info":[{"award-number":["R35GM142726"]}]},{"name":"NIH","award":["R21AG085486"],"award-info":[{"award-number":["R21AG085486"]}]},{"name":"NIH","award":["P20GM125528"],"award-info":[{"award-number":["P20GM125528"]}]},{"name":"NIH","award":["T32AG052363"],"award-info":[{"award-number":["T32AG052363"]}]},{"id":[{"id":"https:\/\/ror.org\/01nbasn20","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,11,29]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Amyloid precursor protein (APP) is a type I transmembrane protein that undergoes proteolytic processing to generate amyloid-\u03b2, the main component of amyloid plaques found in brains with Alzheimer\u2019s disease. The proteolytic processing of APP also generates soluble APP alpha (sAPP\u03b1) which can modulate synaptic transmission and neurite outgrowth through the \u03b3-aminobutyric acid type B receptor (GABA\n                  <jats:sub>B<\/jats:sub>\n                  R). Whether GABA\n                  <jats:sub>B<\/jats:sub>\n                  R mediates functions of sAPP\u03b1 in other neural cell types such as glia remains unknown. sAPP\u03b1 binds the R1a subunit isoform of GABA\n                  <jats:sub>B<\/jats:sub>\n                  R1 which contains two sushi domains absent in R1b. It is unclear whether both GABA\n                  <jats:sub>B<\/jats:sub>\n                  R1 isoforms are expressed equally across brain cell types. We determined relative RNA levels of the GABA\n                  <jats:sub>B<\/jats:sub>\n                  R1a and 1b isoforms in oligodendrocytes, microglia, endothelial cells, astrocytes, and neurons in adult mice using two approaches. We developed a GABA\n                  <jats:sub>B<\/jats:sub>\n                  R1 isoform-specific RNAseq analysis workflow to probe a publicly available dataset. We also isolated five cell types from a single mouse brain and performed RT-qPCR. We show that the GABA\n                  <jats:sub>B<\/jats:sub>\n                  R1a and 1b isoforms are differentially expressed among cell types. GABA\n                  <jats:sub>B<\/jats:sub>\n                  R1a expression was highest in oligodendrocytes and GABA\n                  <jats:sub>B<\/jats:sub>\n                  R1b expression was highest in astrocytes, suggesting that sAPP\u03b1-mediated GABA\n                  <jats:sub>B<\/jats:sub>\n                  R signaling may be most prominent in oligodendrocytes. We also confirmed that APP is expressed in all five cell types and showed that APP RNA levels are highest in oligodendrocytes. Together, our findings uncover cell type-specific expression of GABA\n                  <jats:sub>B<\/jats:sub>\n                  R isoforms and highlight oligodendrocytes as a principal cell type for GABA\n                  <jats:sub>B<\/jats:sub>\n                  R1a-mediated APP signaling, providing a foundation for future mechanistic studies.\n                <\/jats:p>","DOI":"10.1101\/2025.11.25.690528","type":"posted-content","created":{"date-parts":[[2025,11,29]],"date-time":"2025-11-29T17:30:12Z","timestamp":1764437412000},"source":"Crossref","is-referenced-by-count":0,"title":["Oligodendrocytes show enriched expression of amyloid precursor protein and GABA B receptor isoform 1a"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8036-321X","authenticated-orcid":false,"given":"Samah","family":"Houmam","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominika","family":"Siodlak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meena","family":"Seshadri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gideon B.","family":"Hallum","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathan P.","family":"Pezant","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David R.","family":"Stanford","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Casandra","family":"Salinas-Salinas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yvonne M.","family":"Thomason","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Courtney G.","family":"Montgomery","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5818-4338","authenticated-orcid":false,"given":"Heather C.","family":"Rice","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2025120116400750000_2025.11.25.690528v1.1","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2015.01.022"},{"key":"2025120116400750000_2025.11.25.690528v1.2","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-022-02863-x"},{"key":"2025120116400750000_2025.11.25.690528v1.3","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1177\/1073858419882619","article-title":"and Electrical Activity of the Brain","volume":"26","year":"2020","journal-title":"Neuroscientist"},{"key":"2025120116400750000_2025.11.25.690528v1.4","doi-asserted-by":"publisher","DOI":"10.1038\/nrn.2017.29"},{"key":"2025120116400750000_2025.11.25.690528v1.5","doi-asserted-by":"crossref","first-page":"1647","DOI":"10.1042\/BST20221527","article-title":"Amyloid precursor protein and its interacting proteins in neurodevelopment","volume":"51","year":"2023","journal-title":"Biochem Soc Trans"},{"key":"2025120116400750000_2025.11.25.690528v1.6","doi-asserted-by":"crossref","unstructured":"Kruse, P. , Eichler, A. , Klukas, L. & Lenz, M . 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