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

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • D-Aspartic Acid / pharmacology*
  • Hippocampus / drug effects*
  • Long-Term Potentiation / drug effects
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Nerve Tissue Proteins / metabolism*
  • Neuronal Plasticity / drug effects*
  • Receptors, N-Methyl-D-Aspartate / metabolism*
  • Spatial Learning / drug effects
  • Spatial Memory / drug effects*

Substances

  • Gprin1 protein, mouse
  • Nerve Tissue Proteins
  • Receptors, N-Methyl-D-Aspartate
  • D-Aspartic Acid
  • N-methyl D-aspartate receptor subtype 2A