Changes in Cellular Composition of Dentate Gyrus in Response to Intermittent Hypoxia

Abstract

Adult neurogenesis allows for the continual generation of neurons throughout adulthood. It is implicated in the maintenance of normal hippocampal function and is tightly regulated by oxygen homeostasis. Sleep apnea causes periodic cessations in breathing and leads to intermittent hypoxia (IH), which can impair hippocampal based learning and memory. This ongoing study examines how IH influences neural precursors and remodels the neurogenic niche in the hippocampus. We hypothesize that IH destabilizes the pool of intermediate neural progenitors (INPs) and recruits microglia into the area. Our findings indicate that the number of INPs is reduced by IH. Moreover, while IH does not change the number of microglia in the molecular and granular layers of the dentate gyrus, microglia appear to be uniquely recruited into the neurogenic niche (i.e., the subgranular zone) following IH. These findings suggest that IH‐dependent changes in hippocampal adult neurogenesis may stimulate microglial activity which in turn further impact normal hippocampal function. Such effects may play a significant role in influencing hippocampal physiology during untreated sleep apnea. Support or Funding Information This work was supported by NIH PO 1 HL 144454, NIH R01 NS10742101 awarded to AJG, and a grant from The BSD Office of Diversity & Inclusion at The University of Chicago awarded to AJG.

CaMKIIα Expressing Neurons to Report Activity-Related Endogenous Hypoxia upon Motor-Cognitive Challenge

“…In addition, CaMKIIα expression, shown to be important for neuronal maturation in the hippocampus [ 22 ], appeared to be elevated in these cells ( Figure 6 f). Interestingly, previous literature inconsistently reported both negative as well as positive effects of exogenously applied hypoxia on neuronal development, differentiation, and maturation [ 23 , 24 , 25 , 26 , 27 , 28 , 29 ]. Our current findings indicate a positive, stimulating effect on neuronal differentiation, resulting in an increased number of young neurons in CA1.…”