Orexin neuronal changes in the locus coeruleus of the aging rhesus macaque

Orexin neuronal changes in the locus coeruleus of the aging rhesus macaque
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DOI:
10.1016/j.neurobiolaging.2006.05.025
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发表时间:
2007-08-01
影响因子:
4.2
通讯作者:
Urbanski, Henryk F.
Urbanski, Henryk F.
中科院分区:
医学2区
文献类型:
--
作者:
Downs, Jodi L.;Dunn, Michael R.;Urbanski, Henryk F.

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食欲素神经肽调节唤醒状态并兴奋去甲肾上腺素能蓝斑(LC),因此,与年龄相关的食欲素神经元和LC投射的损失可能导致老年人和非人灵长类动物的睡眠质量差。为了验证这一假设,我们研究了在整个生命周期的雄性恒河猴(Macaca mulatta)的外侧下丘脑区(LHA)和LC的食欲素B-mumo反应性。食欲素胞体,主要定位在LHA,表现出相同的分布模式,无论年龄。同样,增食欲素神经元数量和血清增食欲素B浓度也不随年龄而变化。与此相反,食欲素B-免疫反应轴突密度在老年动物的LC显着低于在年轻或成年动物中观察到的。此外,年龄相关的下降与LC中酪氨酸羟化酶(TH)mRNA的显著减少有关,尽管TH-免疫反应神经元数量没有变化。两者合计,这些数据表明,年龄相关的减少兴奋性食欲素神经支配的去甲肾上腺素能LC可能有助于在老年人睡眠质量差的病因。(c)2006年爱思唯尔公司All rights reserved.
Orexin neuropeptides regulate arousal state and excite the noradrenergic locus coerulcus (LC), so it is plausible that an age-related loss of orexin neurons and projections to the LC contributes to poor sleep quality in elderly humans and nonhuman primates. To test this hypothesis we examined orexin B-mmumoreactivity in the lateral hypothalamic area (LHA) and the LC of male rhesus macaques (Macaca mulatta) throughout the life span. Orexin perikarya, localized predominantly in the LHA, showed identical distribution patterns irrespective of age. Similarly, orexin neuron number and serum orexin B concentrations did not differ with age. In contrast, orexin B-immunoreactive axon density in the LC of old animals was significantly lower than that observed in the young or adult animals. Furthermore, the age-related decline was associated with a significant decrease in tyrosine hydroxylase (TH) mRNA in the LC, despite no change in TH-mmumoreactive neuron number. Taken together, these data suggest that age-related decreases in excitatory orexin innervation to the noradrenergic LC may contribute to the etiology of poor sleep quality in the elderly. (c) 2006 Elsevier Inc. All rights reserved.