L型电压依赖性钙通道和兰尼碱受体拮抗剂对老年大鼠空间记忆缺陷的差异性挽救作用。
Differential rescue of spatial memory deficits in aged rats by L-type voltage-dependent calcium channel and ryanodine receptor antagonism.
作者信息
Hopp S C, D'Angelo H M, Royer S E, Kaercher R M, Adzovic L, Wenk G L
机构信息
Department of Neuroscience, Ohio State University, Columbus, OH 43210, USA.
Department of Psychology, Ohio State University, Columbus, OH 43210, USA.
出版信息
Neuroscience. 2014 Nov 7;280:10-8. doi: 10.1016/j.neuroscience.2014.09.007. Epub 2014 Sep 16.
Abstract
Age-associated memory impairments may result as a consequence of neuroinflammatory induction of intracellular calcium (Ca(+2)) dysregulation. Altered L-type voltage-dependent calcium channel (L-VDCC) and ryanodine receptor (RyR) activity may underlie age-associated learning and memory impairments. Various neuroinflammatory markers are associated with increased activity of both L-VDCCs and RyRs, and increased neuroinflammation is associated with normal aging. In vitro, pharmacological blockade of L-VDCCs and RyRs has been shown to be anti-inflammatory. Here, we examined whether pharmacological blockade of L-VDCCs or RyRs with the drugs nimodipine and dantrolene, respectively, could improve spatial memory and reduce age-associated increases in microglia activation. Dantrolene and nimodipine differentially attenuated age-associated spatial memory deficits but were not anti-inflammatory in vivo. Furthermore, RyR gene expression was inversely correlated with spatial memory, highlighting the central role of Ca(+2) dysregulation in age-associated memory deficits.
摘要
与年龄相关的记忆障碍可能是神经炎症诱导细胞内钙（Ca(+2)）调节异常的结果。L型电压依赖性钙通道（L-VDCC）和兰尼碱受体（RyR）活性的改变可能是与年龄相关的学习和记忆障碍的基础。各种神经炎症标志物与L-VDCCs和RyRs活性增加相关，并且神经炎症增加与正常衰老相关。在体外，L-VDCCs和RyRs的药理学阻断已被证明具有抗炎作用。在此，我们分别研究了用药物尼莫地平和丹曲林对L-VDCCs或RyRs进行药理学阻断是否可以改善空间记忆并减少与年龄相关的小胶质细胞激活增加。丹曲林和尼莫地平不同程度地减轻了与年龄相关的空间记忆缺陷，但在体内没有抗炎作用。此外，RyR基因表达与空间记忆呈负相关，突出了Ca(+2)调节异常在与年龄相关的记忆缺陷中的核心作用。
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