{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T13:03:00Z","timestamp":1785416580558,"version":"3.56.0"},"posted":{"date-parts":[[2026,4,7]]},"group-title":"Neuroscience","reference-count":42,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T00:00:00Z","timestamp":1775520000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/publicdomain\/zero\/1.0\/"}],"funder":[{"award":["R01AG071782"],"award-info":[{"award-number":["R01AG071782"]}],"id":[{"id":"https:\/\/ror.org\/049v75w11","id-type":"ROR","asserted-by":"publisher"}]},{"award":["R01AG084473"],"award-info":[{"award-number":["R01AG084473"]}],"id":[{"id":"https:\/\/ror.org\/049v75w11","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,4,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>Insulin-like growth factor-1 (IGF-1) plays a critical role in neuronal signaling. Disrupted insulin\/IGF-1 signaling is implicated in Alzheimer\u2019s disease, among other conditions, yet its specific influence on glutamate receptor-mediated calcium responses remains unclear. We examined the impacts of IGF-1 on glutamate receptor function in primary rat neurons monitored for intraneuronal calcium following stimulation with glutamate, AMPA, or NMDA\/glycine. Pharmacological blockers (CNQX for AMPA receptors, APV for NMDA receptors, and nimodipine for L-type calcium channels) were applied to define receptor-specific contributions. In hippocampal neurons, IGF-1 and insulin altered responses to glutamate in different directions, with IGF-1 tending to evoke and enhanced response. In neocortical neurons, by contrast, IGF-1 consistently reduced glutamate- and AMPA-evoked calcium peaks, suggesting an inhibitory effect on AMPA receptors. To rule out effects on voltage-gated calcium channels downstream of AMPA receptors, we tested effects of IGF-1 on depolarization with potassium chloride; calcium elevation in this case was unaffected by IGF-1. Likewise, IGF-1 did not inhibit responses to NMDA\/glycine; and IGF-1 did not affect glutamate responses in the presence of CNQX, a selective AMPA receptor blocker. These findings, combined with the observation that IGF-1 effects persisted in the presence of APV (an NMDA receptor antagonist), indicate that the inhibition of glutamate responses by IGF-1 is mediated by suppression of AMPA receptor activity. IGF-1 may thus contribute to normal neurophysiology, and given the role that glutamate receptors play in excitotoxicity, IGF-1 may confer neuroprotection in the neocortex. Disruption of IGF-1 signaling, as seen in states resembling insulin resistance, may therefore worsen glutamate-driven excitotoxicity and contribute to adverse outcomes.<\/jats:p>","DOI":"10.64898\/2026.04.04.716504","type":"posted-content","created":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T10:30:20Z","timestamp":1775557820000},"source":"Crossref","is-referenced-by-count":0,"title":["Insulin Growth Factor 1 affects glutamate receptor activity differently in primary cultures of neocortical versus hippocampal neurons"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4111-3944","authenticated-orcid":false,"given":"Urooj","family":"Fatima","sequence":"first","affiliation":[{"name":"Department of Geriatrics, University of Arkansas for Medical Sciences, Little Rock AR 72205, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akshay","family":"Padala","sequence":"additional","affiliation":[{"name":"Department of Geriatrics, University of Arkansas for Medical Sciences, Little Rock AR 72205, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6049-6480","authenticated-orcid":false,"given":"Steven W.","family":"Barger","sequence":"additional","affiliation":[{"name":"Department of Geriatrics, University of Arkansas for Medical Sciences, Little Rock AR 72205, USA"},{"name":"Department of Neuroscience, University of Arkansas for Medical Sciences, Little Rock AR 72205, USA"},{"name":"Geriatric Research Education & Clinical Center, Central Arkansas Veterans Healthcare System, Little Rock AR 72205, 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