背景:阿尔茨海默病(AD)与Aβ的积累有关,tau过度磷酸化增加,持续性神经炎症,和神经营养因子的下降,神经发生,和突触可塑性。催产素(OT)对记忆和学习有显著影响。我们检查了鼻内(IN)OT对突触可塑性的影响,神经发生,组蛋白乙酰化,以及大鼠的空间和认知记忆。
方法:在雄性Wistar大鼠的CA1中连续四天双侧施用Aβ25-35(5µg/2.5µl)。经过7天的恢复,OT(2µg/µl,每个鼻孔10μl)连续7天。工作,空间,和认知记忆,在海马中测量神经发生和突触可塑性相关因子的基因表达。还使用蛋白质印迹法测量组蛋白乙酰化(H3K9和H4K8)。
结果:INOT显着改善了Aβ诱导的工作和空间记忆障碍。参与突触可塑性的因素(MeCP2,REST,突触素,和BDNF)和神经发生(Ki67和DCX)也显着增加了OT的IN给药。我们还发现OT给药后H3K9ac和H4K8ac的水平升高。
结论:这些发现表明INOT可以通过增加突触可塑性来改善海马相关行为,刺激神经发生,和染色质可塑性。
BACKGROUND: Alzheimer\'s disease (AD) is linked to the accumulation of Aβ, increased tau hyperphosphorylation, persistent neuroinflammation, and a decline in neurotrophic factors, neurogenesis, and synaptic plasticity. Oxytocin (OT) has a significant impact on memory and learning. We examined the influence of intranasal (IN) OT on synaptic plasticity, neurogenesis, histone acetylation, and spatial and cognitive memories in rats.
METHODS: Aβ25-35 (5 µg/2.5 µl) was administered bilaterally in the CA1 of male Wistar rats for four consecutive days. After seven days of recovery, OT (2 µg/µl, 10 µl in each nostril) was administered IN for seven consecutive days. Working, spatial, and cognitive memories, and gene expression of neurogenesis- and synaptic plasticity-involved factors were measured in the hippocampus. Histone acetylation (H3K9 and H4K8) was also measured using western blotting.
RESULTS: IN administration of OT significantly improved working and spatial memory impairment induced by Aβ and increased the factors involved in synaptic plasticity (MeCP2, REST, synaptophysin, and BDNF) and neurogenesis (Ki67 and DCX). We also found an enhancement in the levels of H3K9ac and H4K8ac following OT administration.
CONCLUSIONS: These findings indicated that IN OT could improve hippocampus-related behaviors by increasing synaptic plasticity, stimulating neurogenesis, and chromatin plasticity.