Imbalance of synaptic and extrasynaptic NMDA receptors induced by the deletion of CRMP1 accelerates age-related cognitive decline in mice

Yun Chieh Tsai, Sheng Min Huang, Hsu Hsia Peng, Shu Wha Lin, Shu Rung Lin, Ting Yu Chin, Shih Ming Huang

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)

Abstract

Collapsin response mediator protein 1 (CRMP1) is involved in semaphorin 3A signaling pathway, promoting neurite extension and growth cone collapse. It is highly expressed in the nervous system, especially the hippocampus. The crmp1 knockout (KO) mice display impaired spatial learning and memory, and this phenomenon seemingly tends to deteriorate with age. Here we investigated whether CRMP1 is involved in age-related cognitive decline in WT and crmp1 KO mice at adult, middle-aged and older stages. The results revealed that cognitive dysfunction in the Morris water maze task became more severe and decreased glutamate and glutamine level in middle-aged crmp1 KO mice. Additionally, increasing levels of extrasynaptic NMDA receptors and phosphorylation of Tau were observed in middle-aged crmp1 KO mice, leading to synaptic and neuronal loss in the CA3 regions of hippocampus. These findings suggest that deletion of CRMP1 accelerates age-related cognitive decline by disrupting the balance between synaptic and extrasynaptic NMDA receptors, resulting in the loss of synapses and neurons.

Original languageEnglish
Pages (from-to)48-59
Number of pages12
JournalNeurobiology of Aging
Volume135
DOIs
Publication statusPublished - 2024 Mar

All Science Journal Classification (ASJC) codes

  • General Neuroscience
  • Ageing
  • Clinical Neurology
  • Developmental Biology
  • Geriatrics and Gerontology

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