No evidence for cognitive decline or neurodegeneration in strain‐matched Grin3a knockout mice

Abstract

AbstractN‐methyl‐D‐aspartate (NMDA) receptor (NMDAR) dysregulation is thought to contribute to impaired cognition and neurodegeneration in a variety of brain disorders. In a recent article, Zhong et al. proposed that deficiency of the NMDAR subunit GluN3A may be a primary pathogenic factor in sporadic Alzheimer´s disease (AD) based on evidence for degenerative excitotoxicity and cognitive impairment in aging mice lacking GluN3A. Because the result appeared to be at odds with earlier work where genetic GluN3A deletion enhanced learning in younger mice, we have now compared wild‐type and GluN3A knockout mice at later life stages using a congenic mouse strain. Rather than age‐dependent cognitive decline or neurodegeneration, we find that the enhanced performance of young adult GluN3A knockouts in memory tasks persists during aging. In sum, our analysis does not support the hypothesis that GluN3A loss underlies cognitive impairment in AD..