Impaired chemoreflex correlates with decreased c-Fos in respiratory brainstem centers of the streptozotocin-induced Alzheimer's disease rat model

Document Type

Article

Publication Title

Experimental Neurology

Abstract

Besides impairment in cognition and memory, patients with Alzheimer's disease (AD) often exhibit marked dysfunction in respiratory control. Sleep-disordered breathing (SDB) is commonly found in cases of AD, resulting in periods of hypoxia during sleep. Early structural changes in brainstem areas controlling respiratory function may account for SDB in the course of AD. However, to date the underlying mechanisms for these complications are not known. The streptozotocin (STZ)-induced rat model of AD exhibits abnormal responses to hypoxia and increased astrogliosis in a key region for respiratory control. In this study we further defined the pathophysiological respiratory response of STZ-AD rats to 10% O 2 . In addition, we analyzed hypoxia-induced neuronal activation in respiratory and cardiovascular nuclei of the dorsal and ventral brainstem. Two hours of hypoxia induced a transient increase in tidal volume that was followed by a prolonged increase in respiratory rate. Only respiratory rate was significantly blunted in the STZ-AD model, which continued over the entire duration of the hypoxic episode. Analysis of c-Fos expression as a marker for neuronal activation showed abundant labeling throughout the nTS, nuclei of the ventral respiratory column, and A1/C1 cells of cardiovascular centers in the ventral brainstem. STZ-AD rats showed a significant decrease of c-Fos labeling in the caudal/medial nTS, rostral ventral respiratory group, and Bötzinger complex. c-Fos in other respiratory centers and A1/C1 cells was unaltered when compared to control. The results of this study document a region-specific impact of STZ-induced AD in respiratory brainstem nuclei. This decrease in c-Fos expression correlates with the observed blunting of respiration to hypoxia in the STZ-AD rat model.

First Page

285

Last Page

292

DOI

10.1016/j.expneurol.2018.10.012

Publication Date

1-1-2019

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