Chronic intermittent hypoxia alters the dendritic mitochondrial structure and activity in the pre-Bötzinger complex of rats.

Autor: Kang JJ; Department of Neurobiology, The Fourth Military Medical University, Xi'an, China., Fung ML; School of Biomedical Sciences, The University of Hong Kong, Hong Kong, China., Zhang K; Department of Neurobiology, The Fourth Military Medical University, Xi'an, China., Lam CS; School of Biomedical Sciences, The University of Hong Kong, Hong Kong, China., Wu SX; Department of Neurobiology, The Fourth Military Medical University, Xi'an, China., Huang XF; Department of Pathology and Pathophysiology, The Fourth Military Medical University, Xi'an, China., Yang SJ; Department of Pathology and Pathophysiology, The Fourth Military Medical University, Xi'an, China., Wong-Riley MTT; Department of Cell Biology, Neurobiology and Anatomy, Medical College of Wisconsin, Milwaukee, WI, USA., Liu YY; Department of Neurobiology, The Fourth Military Medical University, Xi'an, China.
Jazyk: angličtina
Zdroj: FASEB journal : official publication of the Federation of American Societies for Experimental Biology [FASEB J] 2020 Nov; Vol. 34 (11), pp. 14588-14601. Date of Electronic Publication: 2020 Sep 10.
DOI: 10.1096/fj.201902141R
Abstrakt: Mitochondrial bioenergetics is dynamically coupled with neuronal activities, which are altered by hypoxia-induced respiratory neuroplasticity. Here we report structural features of postsynaptic mitochondria in the pre-Bötzinger complex (pre-BötC) of rats treated with chronic intermittent hypoxia (CIH) simulating a severe condition of obstructive sleep apnea. The subcellular changes in dendritic mitochondria and histochemistry of cytochrome c oxidase (CO) activity were examined in pre-BötC neurons localized by immunoreactivity of neurokinin 1 receptors. Assays of mitochondrial electron transport chain (ETC) complex I, IV, V activities, and membrane potential were performed in the ventrolateral medulla containing the pre-BötC region. We found significant decreases in the mean length and area of dendritic mitochondria in the pre-BötC of CIH rats, when compared to the normoxic control and hypoxic group with daily acute intermittent hypoxia (dAIH) that evokes robust synaptic plasticity. Notably, these morphological alterations were mainly observed in the mitochondria in close proximity to the synapses. In addition, the proportion of mitochondria presented with enlarged compartments and filamentous cytoskeletal elements in the CIH group was less than the control and dAIH groups. Intriguingly, these distinct characteristics of structural adaptability were observed in the mitochondria within spatially restricted dendritic spines. Furthermore, the proportion of moderately to darkly CO-reactive mitochondria was reduced in the CIH group, indicating reduced mitochondrial activity. Consistently, mitochondrial ETC enzyme activities and membrane potential were lowered in the CIH group. These findings suggest that hypoxia-induced respiratory plasticity was characterized by spatially confined mitochondrial alterations within postsynaptic spines in the pre-BötC neurons. In contrast to the robust plasticity evoked by dAIH preconditioning, a severe CIH challenge may weaken the local mitochondrial bioenergetics that the fuel postsynaptic activities of the respiratory motor drive.
(© 2020 Federation of American Societies for Experimental Biology.)
Databáze: MEDLINE
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