Alteration in NMDA Receptor Mediated Glutamatergic Neurotransmission in the Hippocampus During Senescence

Neurochem Res. 2019 Jan;44(1):38-48. doi: 10.1007/s11064-018-2634-4. Epub 2018 Sep 12.


Glutamate is the primary excitatory neurotransmitter in neurons and glia. N-methyl-D-aspartate (NMDA), α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), and kainate receptors are major ionotropic glutamate receptors. Glutamatergic neurotransmission is strongly linked with Ca2+ homeostasis. Research has provided ample evidence that brain aging is associated with altered glutamatergic neurotransmission and Ca2+ dysregulation. Much of the work has focused on the hippocampus, a brain region critically involved in learning and memory, which is particularly susceptible to dysfunction during senescence. The current review examines Ca2+ regulation with a focus on the NMDA receptors in the hippocampus. Integrating the knowledge of the complexity of age-related alterations in Ca2+ homeostasis and NMDA receptor-mediated glutamatergic neurotransmission will positively shape the development of highly effective therapeutics to treat brain disorders including cognitive impairment.

Keywords: Aging; Calcium homeostasis; Glutamatergic neurotransmission; Hippocampus; LTD; LTP; N-Methyl-D-aspartate receptor; Synaptic function.

Publication types

  • Review

MeSH terms

  • Aging
  • Animals
  • Hippocampus / metabolism*
  • Humans
  • Neuroglia / metabolism
  • Neurons / metabolism*
  • Neurotransmitter Agents / metabolism*
  • Receptors, N-Methyl-D-Aspartate / metabolism*
  • Synaptic Transmission / physiology*


  • Neurotransmitter Agents
  • Receptors, N-Methyl-D-Aspartate