Augmenting neurogenesis rescues memory impairments in Alzheimer's disease by restoring the memory-storing neurons.

ABSTRACT: Hippocampal neurogenesis is impaired in Alzheimer's disease (AD) patients and familial Alzheimer's disease (FAD) mouse models. However, it is unknown whether new neurons play a causative role in memory deficits. Here, we show that immature neurons were actively recruited into the engram following a hippocampus-dependent task. However, their recruitment is severely deficient in FAD. Recruited immature neurons exhibited compromised spine density and altered transcript profile. Targeted augmentation of neurogenesis in FAD mice restored the number of new neurons in the engram, the dendritic spine density, and the transcription signature of both immature and mature neurons, ultimately leading to the rescue of memory. Chemogenetic inactivation of immature neurons following enhanced neurogenesis

SUBMITTER: Mishra R 

PROVIDER: S-EPMC9399756 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature