Aging-related alterations in orexin/hypocretin modulation of septo-hippocampal amino acid neurotransmission.
Aging-related alterations in orexin/hypocretin modulation of septo-hippocampal amino acid neurotransmission.
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DOI：
10.1016/j.neuroscience.2011.08.033
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发表时间：
2011-11-10
期刊：
影响因子：
3.3
通讯作者：
Fadel, J. R.
中科院分区：
文献类型：
--
作者：
Stanley, E. M.;Fadel, J. R.
基底前脑内侧隔膜的 GABA 能神经元构成了隔膜海马通路纤维的很大一部分，并且已知可以调节海马氨基酸神经传递并支持认知功能。重要的是，这些神经元还与年龄相关的认知能力下降有关。下丘脑食欲素/下丘脑分泌素神经元支配和调节这些基底前脑神经元的活动，并且还向海马体提供直接输入。然而，食欲素输入在调节海马氨基酸神经传递中的确切作用以及这些相互作用在衰老过程中如何改变尚未明确。在这里，将食欲素 A (OxA) 注射到年轻（3-4 个月）和老年（27-29 个月）Fisher 344 Brown 挪威大鼠的 CA1 和内侧隔膜，并通过体内微透析分析海马 GABA 和谷氨酸流出。 CA1 输注 OxA 后，细胞外 GABA 和谷氨酸流出量增加，但食欲素介导的流出量并未随年龄而改变。然而，内侧隔膜输注 OxA 不会影响年轻大鼠的海马流出，而老年大鼠与年轻大鼠相比，GABA 和谷氨酸流出显着增强。此外，内侧隔膜的免疫组织化学特征显示，老年动物中小清蛋白（PV）阳性细胞体显着减少，隔膜内剩余 GABA 细胞的食欲素纤维神经支配显着减少，而海马的食欲素神经支配并未因衰老过程而改变。这些发现表明：1) OxA 直接调节年轻动物的海马氨基酸神经传递，2) 老年动物对隔膜海马通路的外源性 OxA 激活的反应性增强，3) 老年动物的内侧隔膜 PV 免疫反应性发生内在减少，并且食欲素对剩余隔膜 PV 神经元的神经支配减少。食欲素对隔膜海马活动调节的改变可能导致与年龄相关的觉醒、学习和记忆功能障碍。
GABAergic neurons of the medial septum of the basal forebrain make up a substantial portion of the septo-hippocampal pathway fibers, and are known to modulate hippocampal amino acid neurotransmission and support cognitive function. Importantly, these neurons are also implicated in age-related cognitive decline. Hypothalamic orexin/hypocretin neurons innervate and modulate the activity of these basal forebrain neurons and also provide direct inputs to the hippocampus. However, the precise role of orexin inputs in modulating hippocampal amino acid neurotransmission—as well as how these interactions are altered in aging—has not been defined. Here, orexin A (OxA) was administered to CA1 and the medial septum of young (3–4 months) and aged (27–29 months) Fisher 344 Brown Norway rats, and hippocampal GABA and glutamate efflux was analyzed by in vivo microdialysis. Following CA1 infusion of OxA, extracellular GABA and glutamate efflux was increased, but the magnitude of orexin-mediated efflux was not altered as a function of age. However, medial septum infusion of OxA did not impact hippocampal efflux in young rats, while aged rats exhibited a significant enhancement in GABA and glutamate efflux compared to young counterparts. Furthermore, immunohistochemical characterization of the medial septum revealed a significant decrease in parvalbumin (PV)-positive cell bodies in aged animals, and a significant reduction in orexin fiber innervation to the remaining GABAergic cells within the septum, while orexin innervation to the hippocampus was unaltered by the aging process. These findings indicate that: 1) OxA directly modulates hippocampal amino acid neurotransmission in young animals, 2) Aged animals show enhanced responsivity to exogenous OxA activation of the septo-hippocampal pathway, and, 3) Aged animals undergo an intrinsic reduction in medial septum PV-immunoreactivity, and a decrease in orexin innervation to remaining septal PV neurons. Alterations in orexin regulation of septo-hippocampal activity may contribute to age-related dysfunctions in arousal, learning and memory.
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影响因子：
3.3
作者：
Fadel, J;Pasumarthi, R;Reznikov, LR
通讯作者：
Reznikov, LR
影响因子：
2.5
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2.9
作者：
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3.5
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3.3
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