{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,5]],"date-time":"2026-01-05T21:31:38Z","timestamp":1767648698273},"reference-count":39,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2013,2,12]],"date-time":"2013-02-12T00:00:00Z","timestamp":1360627200000},"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":[[2013,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Although many post\u2010mortem studies have found evidence of central insulin resistance in Alzheimer's disease (AD) patients, results on changes of central insulin\u2010like growth factor\u20101 (IGF\u20101) signaling in the pathological process of AD remain controversial. In the present study, we observed the activation states of IGF\u20101 downstream signaling in brain slices of transgenic mice carrying APPswe\/PS1dE9 mutations (APP\/PS1 mice) at both early and late stages (ex vivo) and further investigated the involvement of oligomeric \u03b2\u2010amyloid (A\u03b2) and A\u03b2\u2010enriched culture medium (CM) on IGF\u20101 sensitivity employing neuronal models (in vitro). In 6\u2010 and 18\u2010month\u2010old APP\/PS1 mice, the phosphorylations of IGF\u20101 receptor (IGF\u20101R) and Akt in response to IGF\u20101 stimulation were significantly reduced in the hippocampal and cortical slices, whereas IGF\u20101R protein expression and mRNA levels of IGF\u20101 and IGF\u20101R in the hippocampal slices were significantly higher than that in wild\u2010type mice. In agreement with these results, reduced IGF\u20101 sensitivity was verified in APP and PS1 double stably transfected CHO cells; moreover, IGF\u20101 stimulated phosphorylations of IGF\u20101R and Akt were also markedly weakened by oligomeric A\u03b2 or A\u03b2\u2010enriched CM posttreatment in CHO cells without APP\/PS1\u2010transfected (K1 cells) and primary hippocampal neurons. These observations indicate that the impaired central IGF\u20101 sensitivity at early and late stages of APP\/PS1 transgenic mice might be attributable, at least partially, to the overproduced A\u03b2, especially the oligomeric A\u03b2. These findings may shed new light on the mechanisms underlying the defective IGF\u20101 signaling in AD pathogenesis and provide important clues for AD drug discovery. \u00a9 2013 Wiley Periodicals, Inc.<\/jats:p>","DOI":"10.1002\/jnr.23201","type":"journal-article","created":{"date-parts":[[2013,2,12]],"date-time":"2013-02-12T09:43:15Z","timestamp":1360662195000},"page":"717-725","source":"Crossref","is-referenced-by-count":23,"title":["Alternations of central insulin\u2010like growth factor\u20101 sensitivity in APP\/PS1 transgenic mice and neuronal models"],"prefix":"10.1002","volume":"91","author":[{"given":"Bing","family":"Zhang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xi Can","family":"Tang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hai 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