{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,27]],"date-time":"2025-10-27T20:33:53Z","timestamp":1761597233171},"reference-count":33,"publisher":"Wiley","issue":"16","license":[{"start":{"date-parts":[[2010,10,8]],"date-time":"2010-10-08T00:00:00Z","timestamp":1286496000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Neuroscience Research"],"published-print":{"date-parts":[[2010,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Hypoxic preconditioning in the brain (HPC), a phenomenon whereby noninjurious hypoxia induces resistance to cell death following ischemia, requires the expression of specific genes. Declines in signal transduction pathway activity with aging may decrease the genomic response to HPC and limit its neuroprotective efficacy. To test this, we determined how signal transduction gene expression, intracellular Ca<jats:sup>2+<\/jats:sup> levels, and phosphorylation of the survival\u2010associated kinase Akt differ in hippocampal slice cultures (HSCs) made from postnatal day 7\u201310 (P7\u201310) and 2\u2010year\u2010old rats following HPC. HPC neuroprotection decreased with increasing source animal age, and HPC could not be demonstrated in HCSs made from animals &gt;6 months of age, despite adjusting the duration of hypoxic exposure. Preconditioning protection required the survival kinase Akt in P10 hippocampal slices cultures. In P9 cultures, HPC increased Akt phosphorylation and the expression of prosurvival genes, including Bcl\u20102, heat shock proteins, protein kinases, c\u2010jun, and Nf\u03baB. Lack of increased Akt phosphorylation and a greatly diminished signaling pathway gene response were found in HSCs from aging animals. Moderate and transient increases in [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub> during HPC occurred in P7\u201310 HSCs, but [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub> was persistently increased at 1 and 24 hr after preconditioning in HSCs from 2\u2010year\u2010old rats. The intracellular Ca<jats:sup>2+<\/jats:sup> chelator BAPTA\u2010AM facilitated HPC neuroprotection in 2\u2010year\u2010old HSCs and restored the pattern of post\u2010HPC gene expression seen in immature animals. We conclude that age\u2010related loss of preconditioning may be due to altered intracellular Ca<jats:sup>2+<\/jats:sup> homeostasis (excess and sustained increase in [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>) and is a lesion that prevents critical elements of neuroprotective signal transduction. \u00a9 2010 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/jnr.22508","type":"journal-article","created":{"date-parts":[[2010,10,8]],"date-time":"2010-10-08T20:07:05Z","timestamp":1286568425000},"page":"3520-3529","source":"Crossref","is-referenced-by-count":22,"title":["Hypoxic preconditioning failure in aging hippocampal neurons: Impaired gene expression and rescue with intracellular calcium chelation"],"prefix":"10.1002","volume":"88","author":[{"given":"Philip E.","family":"Bickler","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christian 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