5-HT6受体激动剂和拮抗剂可改善记忆障碍和MK-801诱导的海马BDNF信号改变。,Brain Research

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5-HT6受体激动剂和拮抗剂可改善记忆障碍和MK-801诱导的海马BDNF信号改变。
Brain Research ( IF 2.7 ) Pub Date : 2019-08-11 , DOI: 10.1016/j.brainres.2019.146375
Joanna Rychtyk ₁ , Anna Partyka ₁ , Joanna Gdula-Argasińska ₂ , Katarzyna Mysłowska ₁ , Natalia Wilczyńska ₁ , Magdalena Jastrzębska-Więsek ₁ , Anna Wesołowska ₁

Affiliation

本研究的目的是研究和比较急性和慢性（21天）5-羟基色胺6受体（5-HT6R）激动剂（WAY-181187）和拮抗剂（SB-742457）的给药效果MK-801在新对象识别（NORT）和Y迷宫连续自发交替测试（Y-CAT）中引起的记忆障碍。此外，在给药21天后测量了大鼠海马中脑源性神经营养因子（BDNF）的表达，以研究BDNF参与5-HT6R配体的促认知作用。我们发现，急性施用WAY-181187和SB-742457可以逆转MK-801在NORT和Y-CAT中的作用，并且长时间在NORT中施用但在Y-CAT中这种影响仍然存在。这两种5-HT6R配体均增加了海马BDNF蛋白的表达，但是WAY-181187比SB-742457更有效，并且可以更好地减轻MK-801对BDNF信号通路的抑制，这似乎在行为测试中转化为更强的WAY-181187效果。总体上，急性和慢性给予的5-HT6R激动剂和拮抗剂均能防止记忆障碍和MK-801诱导的BDNF信号转导的改变。目前的结果证实了两种类型的5-HT6R配体的促认知特性，并表明BDNF途径可能参与其作用机理。预防记忆障碍和MK-801诱导的BDNF信号传导改变。目前的结果证实了两种类型的5-HT6R配体的促认知特性，并表明BDNF途径可能参与其作用机理。预防记忆障碍和MK-801诱导的BDNF信号传导改变。目前的结果证实了两种类型的5-HT6R配体的促认知特性，并表明BDNF途径可能参与其作用机理。

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5-HT6 receptor agonist and antagonist improve memory impairments and hippocampal BDNF signaling alterations induced by MK-801.

The aim of the present study was to investigate and compare the effects of acute and chronic (21-day) administration of agonist (WAY-181187) and antagonist (SB-742457) of the 5-hydroxytryptamine 6 receptor (5-HT6R) on MK-801-induced memory impairments in novel object recognition (NORT) and Y-maze continuous spontaneous alternation tests (Y-CAT). Further, the expression of the brain-derived neurotrophic factor (BDNF) in rat hippocampus was measured after 21-day administration to investigate BDNF participation in the pro-cognitive effects of 5-HT6R ligands. We found that acute administration of WAY-181187, as well as SB-742457, reversed the effects of MK-801 in NORT and Y-CAT, and that this influence persisted after prolonged application in NORT but not in Y-CAT. Both 5-HT6R ligands increased hippocampal BDNF protein expression, but WAY-181187 was much more potent than SB-742457 and alleviated the MK-801-induced inhibition of BDNF signaling pathways better, which seems to translate into a stronger WAY-181187 effect in behavioral tests. Collectively, both the 5-HT6R agonist and the antagonist, administered acutely and chronically, prevent memory impairments and alterations in BDNF signaling induced by MK-801 in rats. The present results confirm the pro-cognitive properties of both types of 5-HT6R ligands and suggest that BDNF pathways may be involved in their mechanism of action.

更新日期：2019-11-01

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