D-天冬氨酸的消耗选择性地促进中期空间记忆和海马 NMDA 受体亚基的表达。

D-Aspartate consumption selectively promotes intermediate-term spatial memory and the expression of hippocampal NMDA receptor subunits.

机构信息

Department of Anatomy, Histology and Embryology, Faculty of Medicine, Semmelweis University, 58 Tűzoltó u, Budapest, 1094, Hungary.

出版信息

Sci Rep. 2021 Mar 17;11(1):6166. doi: 10.1038/s41598-021-85360-w.

Abstract

D-Aspartate (D-Asp) and D-serine (D-Ser) have been proposed to promote early-phase LTP in vitro and to enhance spatial memory in vivo. Here, we investigated the behavioural effects of chronic consumption of D-Asp and D-Ser on spatial learning of mice together with the expression of NMDA receptors. We also studied the alterations of neurogenesis by morphometric analysis of bromo-deoxyuridine incorporating and doublecortin expressing cells in the hippocampus. Our results specify a time period (3-4 h post-training), within which the animals exposed to D-Asp (but not D-Ser) show a more stable memory during retrieval. The cognitive improvement is due to elimination of transient bouts of destabilization and reconsolidation of memory, rather than to enhanced acquisition. D-Asp also protracted reversal learning probably due to reduced plasticity. Expression of GluN1 and GluN2A subunits was elevated in the hippocampus of D-Asp (but not D-Ser) treated mice. D-Asp or D-Ser did not alter the proliferation of neuronal progenitor cells in the hippocampus. The observed learning-related changes evoked by D-Asp are unlikely to be due to enhanced proliferation and recruitment of new neurones. Rather, they are likely associated with an upregulation of NMDA receptors, as well as a reorganization of receptor subunit assemblies in existing hippocampal/dentate neurons.

摘要

D-天冬氨酸(D-Asp)和 D-丝氨酸(D-Ser)被提议用于促进体外早期长时程增强(LTP),并增强体内空间记忆。在这里,我们研究了慢性消耗 D-Asp 和 D-Ser 对小鼠空间学习的行为影响,以及 NMDA 受体的表达。我们还通过溴脱氧尿苷掺入和双皮质素表达细胞的形态计量分析研究了神经发生的变化。我们的结果确定了一个时间窗(训练后 3-4 小时),在此期间,暴露于 D-Asp(而非 D-Ser)的动物在检索过程中表现出更稳定的记忆。认知改善是由于消除了记忆的瞬时不稳定性和再巩固,而不是由于获得能力增强。D-Asp 还延长了反转学习,可能是由于可塑性降低。D-Asp 处理的小鼠海马中 GluN1 和 GluN2A 亚基的表达升高。D-Asp 或 D-Ser 并未改变海马中的神经元祖细胞的增殖。D-Asp 引起的与学习相关的变化不太可能是由于增强了新神经元的增殖和募集。相反,它们可能与 NMDA 受体的上调以及现有海马/齿状回神经元中受体亚基组装的重组有关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3e80/7969773/ac9dc85552d0/41598_2021_85360_Fig1_HTML.jpg

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