Molina Doris P, Ariwodola Olusegun J, Weiner Jeff L, Brunso-Bechtold Judy K, Adams Michelle M
Departments of Neurobiology and Anatomy, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, NC, 27157-1010, USA.
Age (Dordr). 2013 Oct;35(5):1575-87. doi: 10.1007/s11357-012-9460-4. Epub 2012 Aug 1.
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.
与人类一样，在大鼠中，正常衰老的特征是海马体依赖的学习和记忆以及谷氨酸能功能下降。据报道，生长激素（GH）和胰岛素样生长因子-I（IGF-I）水平都会随着年龄增长而降低，用GH或IGF-I进行治疗都可以改善与年龄相关的认知能力下降。有趣的是，急性给予GH和IGF-I可增强幼年动物大鼠海马体中的谷氨酸能突触传递。然而，当通过GH和IGF-I（去IGF-I）改善认知障碍时，这种增强作用在老年大鼠中是否也会出现仍有待确定。为了解决这个问题，我们使用体外海马CA1脑片制备和细胞外记录技术，研究急性给予GH和IGF-I对年轻成年（10个月）和老年（28个月）大鼠复合场兴奋性突触后电位（fEPSP）以及AMPA和NMDA依赖性fEPSP的影响。结果表明，GH和IGF-I在两个年龄组的脑片中均以相似的程度增加了复合、AMPA和NMDA依赖性fEPSP，并且这种增强可能是通过突触后机制介导的。对这些效应背后的信号级联反应的初步表征显示，GH诱导的增强在年轻成年大鼠和老年大鼠中均不是由JAK2信号元件介导的，但IGF-I诱导的增强在老年大鼠中涉及PI3K介导的机制，而在年轻成年大鼠中则不然。目前的研究结果与GH或IGF-I诱导的谷氨酸能传递增强在减轻老年大鼠与年龄相关的认知障碍中所起的作用一致。
