Exogenous growth hormone attenuates cognitive deficits induced by intermittent hypoxia in rats.
Exogenous growth hormone attenuates cognitive deficits induced by intermittent hypoxia in rats.
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DOI：
10.1016/j.neuroscience.2011.08.029
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发表时间：
2011-11-24
期刊：
影响因子：
3.3
通讯作者：
Gozal, D.
中科院分区：
文献类型：
--
作者：
Li, R. C.;Guo, S. Z.;Raccurt, M.;Moudilou, E.;Morel, G.;Brittian, K. R.;Gozal, D.
睡眠呼吸障碍（SDB），其特征是睡眠期间的间歇性缺氧（IH），导致大量的心血管和神经认知并发症，并已成为一个日益严重的公共卫生问题。SDB与生长激素（GH）分泌的抑制有关，生长激素（GH）分泌整体参与中枢神经系统（CNS）的生长、发育和功能。由于GH治疗能够减轻缺氧缺血性卒中模型中的神经认知缺陷，因此在暴露于慢性持续缺氧（CH，10%O2）或间歇性缺氧（IH，每90秒交替10%O2和21%O2）后，在大鼠海马中评估GH、GH受体（GHR）mRNA表达和GH蛋白表达。此外，GH处理（50 µ g/kg，每日s.c.注射）对EPO、VEGF、HO-1和GLUT-1 mRNA表达和神经行为功能的影响。CH显著增加GH mRNA和蛋白表达，以及IGF-1。与此相反，IH仅诱导GH mRNA的中度增加和GH蛋白在第1天略有升高，但IGF-1没有增加。CH，而不是IH，上调GHR mRNA在海马。IH诱导显着的神经认知功能障碍相比，CH或室内空气（RA）。此外，外源性生长激素管理增加海马IGF-1，EPO和VEGF的mRNA表达，不仅减少了IH诱导的海马损伤，而且还减弱了IH诱导的认知缺陷。因此，外源性生长激素可能提供一个可行的治疗干预，以保护IH脆弱的大脑区域从SDB相关的神经元损失和相关的神经认知功能障碍。
Sleep disordered breathing (SDB), which is characterized by intermittent hypoxia (IH) during sleep, causes substantial cardiovascular and neurocognitive complications and has become a growing public health problem. SDB is associated with suppression of growth hormone (GH) secretion, the latter being integrally involved in the growth, development and function of the central nervous system (CNS). Since GH treatment is able to attenuate neurocognitive deficits in a hypoxic-ischemic stroke model, GH, GH receptor (GHR) mRNA expression and GH protein expression were assessed in rat hippocampus after exposures to chronic sustained hypoxia (CH, 10% O2) or intermittent hypoxia (IH, 10% O2 alternating with 21% O2 every 90 sec). In addition, the effect of GH treatment (50 µg/kg, daily s.c. injection) on EPO, VEGF, HO-1 and GLUT-1 mRNA expression and neurobehavioral function was assessed. CH significantly increased GH mRNA and protein expression, as well as IGF-1. In contrast, IH only induced a moderate increase in GH mRNA and a slight elevation in GH protein at day 1, but no increases in IGF-1. CH, but not IH, up-regulated GHR mRNA in the hippocampus. IH induced marked neurocognitive deficits compared to CH or room air (RA). Furthermore, exogenous GH administration increased hippocampal mRNA expression of IGF-1, EPO and VEGF, and not only reduced IH-induced hippocampal injury, but also attenuated IH-induced cognitive deficits. Thus, exogenous GH may provide a viable therapeutic intervention to protect IH-vulnerable brain regions from SDB-associated neuronal loss and associated neurocognitive dysfunction.
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DOI：
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发表时间：
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