Class switching of carbonic anhydrase isoforms mediates remyelination in CA3 hippocampal neurons during chronic hypoxia.

Autor: Barhwal KK; Department of Physiology, All India Institute of Medical Sciences, Bhubaneswar, Odisha, 751019, India. Electronic address: physio_kalpana@aiimsbhubaneswar.edu.in., Biswal S; Centre for Brain Development and Repair, Institute of Stem Cell Biology and Regenerative Medicine, Bangalore, 560065, India; Defence Institute of High Altitude Research, DRDO, C/o 56 APO, Leh-Ladakh, Jammu & Kashmir, 901205, India., Chandra Nag T; Department of Anatomy, All India Institute of Medical Sciences, New Delhi, 110029, India., Chaurasia OP; Defence Institute of High Altitude Research, DRDO, C/o 56 APO, Leh-Ladakh, Jammu & Kashmir, 901205, India., Hota SK; O/o Director General (Life Sciences), DRDO Head Quarters, Rajaji Marg, New Delhi, 110011, India.
Jazyk: angličtina
Zdroj: Free radical biology & medicine [Free Radic Biol Med] 2020 Dec; Vol. 161, pp. 102-114. Date of Electronic Publication: 2020 Oct 06.
DOI: 10.1016/j.freeradbiomed.2020.09.029
Abstrakt: Chronic exposure to hypoxia results in cerebral white matter hyperintensities, increased P300 latency, delayed response and impairment in working memory. Despite burgeoning evidence on role of myelination in nerve conduction, the effect of chronic hypoxia on myelination of hippocampal neurons has been less studied. The present study provides novel evidence on alterations in myelination of hippocampal CA3 neurons following chronic hypoxic exposure. Sprague Dawley rats exposed to global hypobaric hypoxia simulating altitude of 25,000 ft showed progressive demyelination in CA3 hippocampal neurons on 14 days followed by remyelination on 21 and 28 days. The demyelination of CA3 neurons was associated with increased apoptosis of both oligodendrocyte precursor cells (OPCs) and mature oligodendrocytes (OLs), peroxidation of myelin lipids, and nitration induced reduced expression of Carbonic Anhydrase II (CAII). Prolonged hypoxic exposure of 21 and 28 days on the other hand resulted in peroxisome proliferator-activated receptor alpha (PPARα) induced upregulation of Carbonic Anhydrase IV (CAIV) expression in mature oligodendrocytes through iNOS mediated mechanisms along with reduction in lipid peroxidation and remyelination. Inhibition of carbonic anhydrase activity on the other hand prevented remyelination of CA3 neurons. Based on these findings we propose a novel iNOS mediated mechanism for regulation of myelination in hypoxic hippocampal neurons through class switching of carbonic anhydrases.
(Copyright © 2020 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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