Reversal of aging-related emotional memory deficits by norepinephrine via regulating the stability of surface AMPA receptors.
Reversal of aging-related emotional memory deficits by norepinephrine via regulating the stability of surface AMPA receptors.
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DOI：
10.1111/acel.12282
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发表时间：
2015-04
期刊：
影响因子：
7.8
通讯作者：
Wang F
中科院分区：
文献类型：
--
作者：
Luo Y;Zhou J;Li MX;Wu PF;Hu ZL;Ni L;Jin Y;Chen JG;Wang F
与衰老相关的情绪记忆缺陷是阿尔茨海默病和正常衰老的众所周知的并发症。然而，人们对其分子机制知之甚少。为了解决这个问题，我们研究了去甲肾上腺素(NE)及其相关药物地昔帕明对大鼠海马长时程增强(LTP)、AMPA受体表面表达和联合恐惧记忆的调节作用。我们发现老年大鼠在恐惧条件反射过程中存在NE含量和AMPA受体转运的调节缺陷，并伴有情绪记忆和长时程增强。此外，我们还发现，外源性上调NE可通过促进老年大鼠的AMPA受体转运而改善LTP和情绪记忆的损害，而下调NE对成年大鼠LTP的损害。去甲肾上腺素或地塞帕明对老年大鼠情绪记忆损伤有明显的保护作用。这些结果表明去甲肾上腺素在衰老大鼠的突触可塑性和关联恐惧记忆中起着关键作用，提示地塞帕明是治疗衰老相关情绪记忆缺陷的潜在候选药物。
Aging-related emotional memory deficit is a well-known complication in Alzheimer's disease and normal aging. However, little is known about its molecular mechanism. To address this issue, we examined the role of norepinephrine (NE) and its relevant drug desipramine in the regulation of hippocampal long-term potentiation (LTP), surface expression of AMPA receptor, and associative fear memory in rats. We found that there was a defective regulation of NE content and AMPA receptor trafficking during fear conditioning, which were accompanied by impaired emotional memory and LTP in aged rats. Furthermore, we also found that the exogenous upregulation of NE ameliorated the impairment of LTP and emotional memory via enhancing AMPA receptor trafficking in aged rats, and the downregulation of NE impaired LTP in adult rats. Finally, acute treatment with NE or desipramine rescued the impaired emotional memory in aged rats. These results imply a pivotal role for NE in synaptic plasticity and associative fear memory in aging rats and suggest that desipramine is a potential candidate for treating aging-related emotional memory deficit.
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影响因子：
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