Chronic Intermittent Hypoxia-Induced Aberrant Neural Activities in the Hippocampus of Male Rats Revealed by Long-Term in vivo Recording.

Linhao Xu,Wing-Ho Yung,Ya Ke,Qian Li

doi:10.3389/fncel.2021.784045

Abstract

Chronic intermittent hypoxia (CIH) occurs in obstructive sleep apnea (OSA), a common sleep-disordered breathing associated with malfunctions in multiple organs including the brain. How OSA-associated CIH impacts on brain activities and functions leading to neurocognitive impairment is virtually unknown. Here, by means of in vivo electrophysiological recordings via chronically implanted multi-electrode arrays in male rat model of OSA, we found that both putative pyramidal neurons and putative interneurons in the hippocampal CA1 subfield were hyper-excitable during the first week of CIH treatment and followed by progressive suppression of neural firing in the longer term. Partial recovery of the neuronal activities was found after normoxia treatment but only in putative pyramidal neurons. These findings correlated well to abnormalities in dendritic spine morphogenesis of these neurons. The results reveal that hippocampal neurons respond to CIH in a complex biphasic and bidirectional manner eventually leading to suppression of firing activities. Importantly, these changes are attributed to a larger extent to impaired functions of putative interneurons than putative pyramidal neurons. Our findings therefore revealed functional and structural damages in central neurons in OSA subjects.

Highlights

Obstructive sleep apnea (OSA), a common sleep-disordered breathing, is associated with intermittent hypoxia resulting from upper airway obstruction of structural or neural causes (Mathieu et al, 2008)
To mimic OSA-associated intermittent hypoxia, rats were placed in specially designed chambers and exposed to intermittent hypoxia paradigm consisting of cycling oxygen levels between 10 and 21% in 90s for 8 h (Figure 1A)
Based on the duration of the spikes and their frequencies, two populations of neurons were found with properties that are consistent with the principal, pyramidal neurons and interneurons reported previously (Csicsvari et al, 1999; Hussaini et al, 2011)

Summary

Introduction

Obstructive sleep apnea (OSA), a common sleep-disordered breathing, is associated with intermittent hypoxia resulting from upper airway obstruction of structural or neural causes (Mathieu et al, 2008). Significant changes in the gray matter and white matter are often found in the hippocampal area in both adult and children OSA subjects (Macey et al, 2002; Morrell et al, 2010; Torelli et al, 2011; Cha et al, 2017; Song et al, 2018; Owen et al, 2019). How intermittent hypoxia that occurs in OSA impacts on the neurons in the hippocampus or other brain areas are far from clear

Methods

Results

Conclusion