Pharmacologically induced impairment of neurovascular coupling responses alters gait coordination in mice.
Pharmacologically induced impairment of neurovascular coupling responses alters gait coordination in mice.
复制标题
药理诱导的神经血管耦合反应损伤会改变小鼠的步态协调性。
DOI：
10.1007/s11357-017-0003-x
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发表时间：
2017
期刊：
影响因子：
5.6
通讯作者：
Ungvari,Zoltan
中科院分区：
文献类型：
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作者：
Tarantini,Stefano;Yabluchanksiy,Andriy;Fülöp,GáborA;Hertelendy,Peter;Valcarcel-Ares,MNoa;Kiss,Tamas;Bagwell,JonathanM;O'Connor,Daniel;Farkas,Eszter;Sorond,Farzaneh;Csiszar,Anna;Ungvari,Zoltan
有相关证据表明，受损的脑血流量（CBF）调节，除了促进认知障碍，也与步态的改变和老年人福尔斯的发展。CBF通过神经血管偶联（NVC）调节神经元活动，该机制随着年龄的增长而逐渐受损。为了建立NVC受损和步态异常之间的直接因果关系，我们通过抑制NVC中涉及的血管舒张介质的合成来诱导年轻C57 BL/6小鼠的神经血管解偶联。用环氧酶抑制剂MSPPOH、NO合成酶抑制剂L-NAME和考克斯抑制剂吲哚美辛治疗小鼠，可显著降低NVC，模拟衰老表型。药理学诱导的神经血管解偶联显著降低了动态步态参数占空比，改变了脚步模式，并显著增加了相位离散度，表明肢体间协调受损。受损的NVC也倾向于增加步态变异性。因此，NVC的选择性实验中断导致亚临床步态异常，支持CBF在认知功能和步态调节中的重要性。
There is correlative evidence that impaired cerebral blood flow (CBF) regulation, in addition to promoting cognitive impairment, is also associated with alterations in gait and development of falls in elderly people. CBF is adjusted to neuronal activity via neurovascular coupling (NVC) and this mechanism becomes progressively impaired with age. To establish a direct cause-and-effect relationship between impaired NVC and gait abnormalities, we induced neurovascular uncoupling pharmacologically in young C57BL/6 mice by inhibiting the synthesis of vasodilator mediators involved in NVC. Treatment of mice with the epoxygenase inhibitor MSPPOH, the NO synthase inhibitor L-NAME, and the COX inhibitor indomethacin significantly decreased NVC mimicking the aging phenotype. Pharmacologically induced neurovascular uncoupling significantly decreased the dynamic gait parameter duty cycle, altered footfall patterns, and significantly increased phase dispersion, indicating impaired interlimb coordination. Impaired NVC also tended to increase gait variability. Thus, selective experimental disruption of NVC causes subclinical gait abnormalities, supporting the importance of CBF in both cognitive function and gait regulation.