Cognitive impairment in a rat model of neuropathic pain: role of hippocampal microtubule stability.
Cognitive impairment in a rat model of neuropathic pain: role of hippocampal microtubule stability.
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DOI：
10.1097/j.pain.0000000000001233
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发表时间：
2018-08
期刊：
影响因子：
7.4
通讯作者：
Mao J
中科院分区：
文献类型：
--
作者：
You Z;Zhang S;Shen S;Yang J;Ding W;Yang L;Lim G;Doheny JT;Tate S;Chen L;Mao J
临床证据表明，认知障碍是慢性疼痛的常见共病。然而，慢性疼痛介导的认知障碍的细胞基础仍然不清楚。我们在这里报告，大鼠表现出记忆缺陷后，幸免于难的伤害（SNI）。我们发现记忆障碍大鼠海马稳定微管（MT）水平增加。这种稳定MT的增加以α-微管蛋白过度乙酰化为标志。药理学MT稳定剂Paclitazone可增加正常大鼠海马中稳定的MT水平，并诱导学习和记忆障碍。此外，紫杉醇减少海马脑片的长时程增强（LTP），增加海马神经元细胞中稳定的MT（由α-微管蛋白过度乙酰化证明）水平。侧脑室注射MT去稳定剂诺考达唑可改善SNI诱导的伤害性行为大鼠的记忆障碍。HDAC 6是一种α-微管蛋白去乙酰化酶，在认知障碍大鼠的海马中表达减少。这些结果表明，周围神经损伤（如SNI）影响MT的动态平衡，这是至关重要的神经元结构和突触可塑性。
Clinical evidence indicates that cognitive impairment is a common comorbid condition of chronic pain. However, the cellular basis for chronic pain-mediated cognitive impairment remains unclear. We report here that rats exhibited memory deficits after spared never injury (SNI). We found that levels of stable microtubule (MT) were increased in the hippocampus of the rats with memory deficits. This increase in stable MT is marked by α-tubulin hyperacetylation. Paclitaxel, a pharmacological MT stabilizer, increased the level of stable MT in the hippocampus and induced learning and memory deficits in normal rats. Furthermore, paclitaxel reduced long-term potentiation (LTP) in hippocampal slices and increased stable MT (evidenced by α-tubulin hyperacetylation) levels in hippocampal neuronal cells. Intracerebroventricular infusion of nocodazole, a MT destabilizer, ameliorated memory deficits in rats with SNI induced nociceptive behavior. Expression of HDAC6, an α-tubulin deacetylase, was reduced in the hippocampus in rats with cognitive impairment. These findings indicate that peripheral nerve injury (e.g. SNI) affects the MT dynamic equilibrium, which is critical to neuronal structure and synaptic plasticity.
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DOI：
10.1093/jnen/62.12.1211
发表时间：
2003-12-01
影响因子：
3.2
作者：
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