title: Growth hormone and insulin-like growth factor-I alter hippocampal excitatory synaptic transmission in young and old rats.
abstract: In rats, as in humans, normal aging is characterized by a decline in hippocampal-dependent learning and memory, as well as in glutamatergic function. Both growth hormone (GH) and insulin-like growth factor-I (IGF-I) levels have been reported to decrease with age, and treatment with either GH or IGF-I can ameliorate age-related cognitive decline. Interestingly, acute GH and IGF-I treatments enhance glutamatergic synaptic transmission in the rat hippocampus of juvenile animals. However, whether this enhancement also occurs in old rats, when cognitive impairment is ameliorated by GH and IGF-I (des-IGF-I), remains to be determined. To address this issue, we used an in vitro CA1 hippocampal slice preparation and extracellular recording techniques to study the effects of acute application of GH and IGF-I on compound field excitatory postsynaptic potentials (fEPSPs), as well as AMPA- and NMDA-dependent fEPSPs, in young adult (10 months) and old (28 months) rats. The results indicated that both GH and IGF-I increased compound-, AMPA-, and NMDA-dependent fEPSPs to a similar extent in slices from both age groups and that this augmentation was likely mediated via a postsynaptic mechanism. Initial characterization of the signaling cascades underlying these effects revealed that the GH-induced enhancement was not mediated by the JAK2 signaling element in either young adult or old rats but that the IGF-I-induced enhancement involved a PI3K-mediated mechanism in old, but not young adults. The present findings are consistent with a role for a GH- or IGF-I-induced enhancement of glutamatergic transmission in mitigating age-related cognitive impairment in old rats.
authors.affiliation: Departments of Neurobiology and Anatomy, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, NC, 27157-1010, USA.
authors.forename: Doris P
authors.initials: DP
authors.lastname: Molina
authors.forename: Olusegun J
authors.initials: OJ
authors.lastname: Ariwodola
authors.forename: Jeff L
authors.initials: JL
authors.lastname: Weiner
authors.forename: Judy K
authors.initials: JK
authors.lastname: Brunso-Bechtold
authors.forename: Michelle M
authors.initials: MM
authors.lastname: Adams
mesh_terms: D000375:Aging / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D003072:Cognition Disorders / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D004195:Disease Models, Animal; D013006:Growth Hormone / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D008297:Male; D051381:Rats; D011914:Rats, Inbred BN; D011916:Rats, Inbred F344; D009435:Synaptic Transmission / Q000187:drug effects
chemical_list: D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone