{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T13:28:19Z","timestamp":1790515699733,"version":"4.1.0"},"reference-count":62,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2003,9,12]],"date-time":"2003-09-12T00:00:00Z","timestamp":1063324800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Neurochemistry"],"published-print":{"date-parts":[[2003,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Positron emission tomography studies in major depression show reduced serotonin (5\u2010HT)<jats:sub>1A<\/jats:sub> receptor antagonist\u2010binding potentials in many brain regions including occipital cortex. The functional meaning of this observation in terms of signal transduction is unknown. We used postmortem brain samples from depressed suicide victims to examine the downstream effectors of 5\u2010HT<jats:sub>1A<\/jats:sub> receptor activation. The diagnosis was established by means of psychological autopsy using Diagnostic and Statistical Manual of Mental Disorders (DSM) III\u2010R criteria. Measurements of [<jats:sup>35<\/jats:sup>S]GTP\u03b3S binding to G\u03b1i\/o in the occipital cortex of suicide victims and matched controls revealed a blunted response in suicide subjects and a decrease in the coupling of 5\u2010HT<jats:sub>1A<\/jats:sub> receptor to adenylyl cyclase. No significant group differences were detected in the expression levels of G\u03b1i\/o, G\u03b1q\/11 or G\u03b1s proteins, or in the activity of cAMP\u2010dependent protein kinase A. Studies of a parallel transduction pathway downstream from 5\u2010HT<jats:sub>1A<\/jats:sub> receptor activation demonstrated a decrease in the activity of phosphatidylinositol 3\u2010kinase and its downstream effector Akt, as well as an increase in PTEN (phosphatase and tensin homolog deleted on chromosome 10), the phosphatase that hydrolyzes phosphatidylinositol 3,4,5\u2010triphosphate. Finally, the activation of extracellular signal\u2010regulated kinases 1 and 2 was attenuated in suicide victims. These data suggest that the alterations in agonist\u2010stimulated 5\u2010HT<jats:sub>1A<\/jats:sub> receptor activation in depressed suicide victims are also manifest downstream from the associated G protein, affecting the activity of second messengers in two 5\u2010HT<jats:sub>1A<\/jats:sub> receptor transduction pathways that may have implications for cell survival.<\/jats:p>","DOI":"10.1046\/j.1471-4159.2003.01987.x","type":"journal-article","created":{"date-parts":[[2003,9,12]],"date-time":"2003-09-12T11:55:21Z","timestamp":1063367721000},"page":"182-194","source":"Crossref","is-referenced-by-count":129,"title":["Attenuated 5\u2010HT<sub>1A<\/sub> receptor signaling in brains of suicide victims: involvement of adenylyl cyclase, phosphatidylinositol 3\u2010kinase, Akt and mitogen\u2010activated protein kinase"],"prefix":"10.1111","volume":"87","author":[{"given":"Shu\u2010chi","family":"Hsiung","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mella","family":"Adlersberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victoria","family":"Arango","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. 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