Reduced neuroplasticity in aged rats: a role for the neurotrophin brain-derived neurotrophic factor
Reduced neuroplasticity in aged rats: a role for the neurotrophin brain-derived neurotrophic factor
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DOI：
10.1016/j.neurobiolaging.2013.06.014
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发表时间：
2013-12-01
影响因子：
4.2
通讯作者：
Riva, Marco A.
中科院分区：
文献类型：
--
作者：
Calabrese, Francesca;Guidotti, Gianluigi;Riva, Marco A.
衰老是一个生理过程，其特征是神经元可塑性的显著降低，这可能有助于在老年受试者中观察到的功能缺陷。即使导致这种损伤的神经生物学机制仍然在很大程度上未知，神经营养分子的作用，如神经营养蛋白脑源性神经营养因子（BDNF），已被假定。在此基础上，本研究的目的是提供详细的调查，在转录和翻译水平上的BDNF系统，腹侧和背侧海马和前额叶皮层的中老年大鼠，与成年动物相比。还分析了BDNF调节和反应中主要参与者的表达，包括转录因子、钙响应性转录因子、环磷酸腺苷（cAMP）响应元件结合蛋白（CREB）、神经元Per Arnt Sim（PAS）结构域蛋白4和高亲和力受体原肌球蛋白受体激酶B（Trk B）。我们的研究结果表明，BDNF系统在不同水平的影响，在老年大鼠与全球损害，包括减少转录，受损的蛋白质合成和加工，减少激活的TrkB受体。这些修饰可能导致与衰老相关的认知缺陷，并表明旨在恢复减少的神经营养作用的药理学策略可能有助于抵消与年龄相关的认知下降。(C)2013 Elsevier Inc. All rights reserved.
Aging is a physiological process characterized by a significant reduction of neuronal plasticity that might contribute to the functional defects observed in old subjects. Even if the neurobiological mechanisms that contribute to such impairment remain largely unknown, a role for neurotrophic molecules, such as the neurotrophin brain-derived neurotrophic factor (BDNF), has been postulated. On this basis, the purpose of this study was to provide a detailed investigation of the BDNF system, at transcriptional and translational levels, in the ventral and dorsal hippocampus and in the prefrontal cortex of middle-aged and old rats, compared with in adult animals. The expression of major players in BDNF regulation and response, including the transcription factors, calcium-responsive transcription factor, cyclic adenosine monophosphate (cAMP) responsive element-binding protein (CREB), and neuronal Per Arnt Sim (PAS) domain protein 4, and the high-affinity receptor tropomyosin receptor kinase B (TrkB), was also analyzed. Our results demonstrate that the BDNF system is affected at different levels in aged rats with global impairment including reduced transcription, impaired protein synthesis and processing, and decreased activation of the TrkB receptors. These modifications might contribute to the cognitive deficits associated with aging and suggest that pharmacological strategies aimed at restoring reduced neurotrophism might be useful to counteract age-related cognitive decline. (C) 2013 Elsevier Inc. All rights reserved.