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首页> 外文期刊>Advances in Alzheimer's Disease >Rivastigmine Restores 5-HT1A Receptor Levels in the Hippocampus of Olfactory Bulbectomized Mice
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Rivastigmine Restores 5-HT1A Receptor Levels in the Hippocampus of Olfactory Bulbectomized Mice

机译：Rivastigmine可恢复嗅球切除小鼠海马中的5-HT1A受体水平。

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Rivastigmine, a dual acetylcholinesterase and butyrylcholinesterase inhibitor, is used for symptomatic treatment of patients with mild to moderately severe dementia in Alzheimer’s disease (AD) patients. In the present study, we found that 5-HT1A receptor (5-HT1AR) is downregulated, whereas 5-HT2A receptor (5-HT2AR) is upregulated in the hippocampal dentate gyrus (DG) and CA1 region by olfactory bulbectomy (OBX) in mice. Furthermore, chronic treatment with rivastigmine (1.0 mg/kg) for 2 weeks starting 2 weeks after OBX operation restored the decreased 5-HT1AR and the increased 5-HT2AR levels. To determine whether cholinergic receptor stimulation by rivastigmine is involved in the rivastigmine-induced regulation of 5-HTR levels, we treated the mice with mecamylamine (2.5 mg/kg), or atropine (5.0 mg/kg) with rivastigmine (1.0 mg/kg) once a day for 2 weeks. Notably, the rivastigmine-induced 5-HT1AR upregulation was eliminated by mecamylamine but not by atropine treatments. On the other hand, the restored 5-HT2AR level by rivastigmine was not affected by either mecamylamine or atropine. Treatment with 8-OH-DPAT, a selective 5-HT1AR agonist improved the decreased 5-HT1AR and the increased 5-HT2AR levels in OBX mice. On the other hand, treatment with TCB-2, a potent 5-HT2AR agonist had no effects on the 5-HT1AR and 5-HT2AR dysregulation in OBX mice. Taken together, nicotinic acetylcholine receptor (nAChR) stimulation mediates rivastigmine-induced upregulation of 5-HT1AR. Therefore, we speculate that the increased ACh levels by rivastigmine can stimulate nAChR located on serotonergic nerve terminals and stimulate 5-HT1AR by the enhanced 5-HT release in the hippocampus. The 5-HT1AR stimulation likely mediates the improvement of 5-HT1AR levels as auto-receptor in OBX hippocampus.
机译：Rivastigmine是一种乙酰胆碱酯酶和丁酰胆碱酯酶的双重抑制剂，用于对阿尔茨海默病（AD）患者的轻度至中度重度痴呆症患者进行对症治疗。在本研究中，我们发现嗅球切除术（OBX）在海马齿状回（DG）和CA1区中5-HT1A受体（5-HT1AR）被下调，而5-HT2A受体（5-HT2AR）被上调。老鼠。此外，在OBX手术后2周开始，用rivastigmine（1.0 mg / kg）进行2周的慢性治疗可恢复降低的5-HT1AR和升高的5-HT2AR水平。为了确定rivastigmine刺激胆碱能受体是否参与了rivastigmine诱导的5-HTR水平调节，我们用美卡敏胺（2.5 mg / kg）或阿托品（5.0 mg / kg）与rivastigmine（1.0 mg / kg）处理了小鼠），每天一次，持续2周。值得注意的是，美卡明胺消除了利伐斯的明诱导的5-HT1AR上调，但阿托品治疗则没有。另一方面，利伐斯的明恢复的5-HT2AR水平不受美加明胺或阿托品的影响。用8-OH-DPAT，选择性5-HT1AR激动剂治疗可改善OBX小鼠体内降低的5-HT1AR和升高的5-HT2AR水平。另一方面，用强力的5-HT2AR激动剂TCB-2处理对OBX小鼠的5-HT1AR和5-HT2AR失调没有影响。两者合计，烟碱乙酰胆碱受体（nAChR）刺激介导利凡斯的明诱导的5-HT1AR上调。因此，我们推测，rivastigmine增加的ACh水平可以刺激位于血清素能神经末梢的nAChR，并通过增强的海马5-HT释放来刺激5-HT1AR。 5-HT1AR刺激可能介导了OBX海马中5-HT1AR水平作为自身受体的改善。

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