Age-Dependent Impairment of Neurovascular and Neurometabolic Coupling in the Hippocampus.
Age-Dependent Impairment of Neurovascular and Neurometabolic Coupling in the Hippocampus.
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DOI：
10.3389/fphys.2018.00913
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发表时间：
2018
影响因子：
4
通讯作者：
Laranjinha J
中科院分区：
文献类型：
--
作者：
Lourenço CF;Ledo A;Caetano M;Barbosa RM;Laranjinha J
神经血管和神经代谢耦合是大脑功能的关键和复杂的过程。这些过程的调节扰动可能是病理性脑老化和年龄相关性神经变性的早期功能障碍性改变。有证据支持一氧化氮（·NO）在神经血管耦合（通过从神经元到血管的信号传导）和神经代谢耦合（通过调节线粒体对O2的利用）中作为关键信使的作用。在本研究中，我们研究了神经血管和神经代谢耦合的功能与·NO信号传导以及与衰老过程中的认知表现的关系。为此，我们在体内进行了同步测量·NO，O2和脑血流量（CBF）在F344大鼠海马沿着实足年龄的反应，海马神经元激活和认知性能的相关性。首先，证明了谷氨酸刺激海马齿状回后的事件的时间顺序，包括局部和短暂的·NO增加，随后是短暂的局部CBF和pO2变化。具体而言，·NO的瞬时增加之后是CBF的增加和局部pO2的双相变化。我们观察到，虽然谷氨酸诱导的·NO动力学不受衰老的显著影响，但相应的血流动力学随着学习和记忆的下降而逐渐减少。值得注意的是，尽管血液供应受损，但在老年大鼠中，我们观察到与血流动力学反应相关的ΔpO2增加，表明O2的总体代谢率降低。此外，在F344大鼠中观察到的沿着衰老的神经血管偶联损伤在年轻大鼠中通过促进氧化还原状态的不平衡通过细胞内产生超氧自由基而被模仿。这一观察结果加强了氧化应激可能在脑老化和功能障碍的神经血管解偶联中起关键作用的观点。总的来说，数据支持与认知下降有关的神经血管反应受损，这是由于衰老期间氧化环境依赖性受损的·NO信号从神经元到血管。
Neurovascular and neurometabolic coupling are critical and complex processes underlying brain function. Perturbations in the regulation of these processes are, likely, early dysfunctional alterations in pathological brain aging and age-related neurodegeneration. Evidences support the role of nitric oxide (•NO) as a key messenger both in neurovascular coupling, by signaling from neurons to blood vessels, and in neurometabolic coupling, by modulating O2 utilization by mitochondria. In the present study, we investigated the functionality of neurovascular and neurometabolic coupling in connection to •NO signaling and in association to cognitive performance during aging. For this, we performed in vivo simultaneous measurements of •NO, O2 and cerebral blood flow (CBF) in the hippocampus of F344 rats along chronological age in response to glutamatergic activation and in correlation with cognitive performance. Firstly, it is evidenced the temporal sequence of events upon glutamate stimulation of hippocampal dentate gyrus, encompassing the local and transitory increase of •NO followed by transitory local changes of CBF and pO2. Specifically, the transient increase of •NO is followed by an increase of CBF and biphasic changes of the local pO2. We observed that, although the glutamate-induced •NO dynamics were not significantly affected by aging, the correspondent hemodynamic was progressively diminished accompanying a decline in learning and memory. Noteworthy, in spite of a compromised blood supply, in aged rats we observed an increased ΔpO2 associated to the hemodynamic response, suggestive of a decrease in the global metabolic rate of O2. Furthermore, the impairment in the neurovascular coupling observed along aging in F344 rats was mimicked in young rats by promoting an unbalance in redox status toward oxidation via intracellular generation of superoxide radical. This observation strengthens the idea that oxidative stress may have a critical role in the neurovascular uncoupling underlying brain aging and dysfunction. Overall, data supports an impairment of neurovascular response in connection with cognition decline due to oxidative environment-dependent compromised •NO signaling from neurons to vessels during aging.
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影响因子：
5.5
作者：
Cooper, Chris E.;Giulivi, Cecilia
通讯作者：
Giulivi, Cecilia
影响因子：
4.2
作者：
Dias, Candida;Lourenco, Catia F.;Ledo, Ana
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影响因子：
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作者：
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影响因子：
4.8
作者：
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影响因子：
4.2
作者：
Desjardins, Michele;Berti, Romain;Lesage, Frederic
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