Chemogenetic activation of astrocytes promotes remyelination and restores cognitive deficits in visceral hypersensitive rats

Summary: Using a well-established chronic visceral hypersensitivity (VH) rat model, we characterized the decrease of myelin basic protein, reduced number of mature oligodendrocytes (OLs), and hypomyelination in the anterior cingulate cortex (ACC). The results of rat gambling test showed impaired dec...

Full description

Bibliographic Details
Main Authors: Mahadi Hasan, Zhuogui Lei, Mastura Akter, Zafar Iqbal, Faeeqa Usaila, Aruna Surendran Ramkrishnan, Ying Li
Format: Article
Language:English
Published: Elsevier 2023-01-01
Series:iScience
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2589004222021137
_version_ 1828057103475933184
author Mahadi Hasan
Zhuogui Lei
Mastura Akter
Zafar Iqbal
Faeeqa Usaila
Aruna Surendran Ramkrishnan
Ying Li
author_facet Mahadi Hasan
Zhuogui Lei
Mastura Akter
Zafar Iqbal
Faeeqa Usaila
Aruna Surendran Ramkrishnan
Ying Li
author_sort Mahadi Hasan
collection DOAJ
description Summary: Using a well-established chronic visceral hypersensitivity (VH) rat model, we characterized the decrease of myelin basic protein, reduced number of mature oligodendrocytes (OLs), and hypomyelination in the anterior cingulate cortex (ACC). The results of rat gambling test showed impaired decision-making, and the results of electrophysiological studies showed desynchronization in the ACC to basolateral amygdala (BLA) neural circuitry. Astrocytes release various factors that modulate oligodendrocyte progenitor cell proliferation and myelination. Astrocytic Gq-modulation through expression of hM3Dq facilitated oligodendrocyte progenitor cell proliferation and OL differentiation, and enhanced ACC myelination in VH rats. Activating astrocytic Gq rescued impaired decision-making and desynchronization in ACC-BLA. These data indicate that ACC hypomyelination is an important component of impaired decision-making and network desynchronization in VH. Astrocytic Gq activity plays a significant role in oligodendrocyte myelination and decision-making behavior in VH. Insights from these studies have potential for interventions in myelin-related diseases such as chronic pain-associated cognitive disorders.
first_indexed 2024-04-10T21:06:03Z
format Article
id doaj.art-07250e4819b94a8491e1b89b7fcdd298
institution Directory Open Access Journal
issn 2589-0042
language English
last_indexed 2024-04-10T21:06:03Z
publishDate 2023-01-01
publisher Elsevier
record_format Article
series iScience
spelling doaj.art-07250e4819b94a8491e1b89b7fcdd2982023-01-22T04:41:25ZengElsevieriScience2589-00422023-01-01261105840Chemogenetic activation of astrocytes promotes remyelination and restores cognitive deficits in visceral hypersensitive ratsMahadi Hasan0Zhuogui Lei1Mastura Akter2Zafar Iqbal3Faeeqa Usaila4Aruna Surendran Ramkrishnan5Ying Li6Department of Neuroscience, City University of Hong Kong, Hong Kong SAR, China; Department of Biomedical Sciences, City University of Hong Kong, Hong Kong SAR, ChinaDepartment of Neuroscience, City University of Hong Kong, Hong Kong SAR, China; Department of Biomedical Sciences, City University of Hong Kong, Hong Kong SAR, China; Centre for Regenerative Medicine and Health, Hong Kong Institute of Science & Innovation, Chinese Academy of Sciences, Hong Kong SAR, ChinaDepartment of Neuroscience, City University of Hong Kong, Hong Kong SAR, China; Department of Biomedical Sciences, City University of Hong Kong, Hong Kong SAR, ChinaDepartment of Neuroscience, City University of Hong Kong, Hong Kong SAR, China; Department of Biomedical Sciences, City University of Hong Kong, Hong Kong SAR, China; Centre for Regenerative Medicine and Health, Hong Kong Institute of Science & Innovation, Chinese Academy of Sciences, Hong Kong SAR, ChinaDepartment of Neuroscience, City University of Hong Kong, Hong Kong SAR, China; Department of Biomedical Sciences, City University of Hong Kong, Hong Kong SAR, ChinaDepartment of Neuroscience, City University of Hong Kong, Hong Kong SAR, China; Department of Biomedical Sciences, City University of Hong Kong, Hong Kong SAR, ChinaDepartment of Neuroscience, City University of Hong Kong, Hong Kong SAR, China; Department of Biomedical Sciences, City University of Hong Kong, Hong Kong SAR, China; Centre for Regenerative Medicine and Health, Hong Kong Institute of Science & Innovation, Chinese Academy of Sciences, Hong Kong SAR, China; Centre for Biosystems, Neuroscience, and Nanotechnology, City University of Hong Kong, Hong Kong SAR, China; Corresponding authorSummary: Using a well-established chronic visceral hypersensitivity (VH) rat model, we characterized the decrease of myelin basic protein, reduced number of mature oligodendrocytes (OLs), and hypomyelination in the anterior cingulate cortex (ACC). The results of rat gambling test showed impaired decision-making, and the results of electrophysiological studies showed desynchronization in the ACC to basolateral amygdala (BLA) neural circuitry. Astrocytes release various factors that modulate oligodendrocyte progenitor cell proliferation and myelination. Astrocytic Gq-modulation through expression of hM3Dq facilitated oligodendrocyte progenitor cell proliferation and OL differentiation, and enhanced ACC myelination in VH rats. Activating astrocytic Gq rescued impaired decision-making and desynchronization in ACC-BLA. These data indicate that ACC hypomyelination is an important component of impaired decision-making and network desynchronization in VH. Astrocytic Gq activity plays a significant role in oligodendrocyte myelination and decision-making behavior in VH. Insights from these studies have potential for interventions in myelin-related diseases such as chronic pain-associated cognitive disorders.http://www.sciencedirect.com/science/article/pii/S2589004222021137Biological sciencesCognitive neuroscienceNeuroscience
spellingShingle Mahadi Hasan
Zhuogui Lei
Mastura Akter
Zafar Iqbal
Faeeqa Usaila
Aruna Surendran Ramkrishnan
Ying Li
Chemogenetic activation of astrocytes promotes remyelination and restores cognitive deficits in visceral hypersensitive rats
iScience
Biological sciences
Cognitive neuroscience
Neuroscience
title Chemogenetic activation of astrocytes promotes remyelination and restores cognitive deficits in visceral hypersensitive rats
title_full Chemogenetic activation of astrocytes promotes remyelination and restores cognitive deficits in visceral hypersensitive rats
title_fullStr Chemogenetic activation of astrocytes promotes remyelination and restores cognitive deficits in visceral hypersensitive rats
title_full_unstemmed Chemogenetic activation of astrocytes promotes remyelination and restores cognitive deficits in visceral hypersensitive rats
title_short Chemogenetic activation of astrocytes promotes remyelination and restores cognitive deficits in visceral hypersensitive rats
title_sort chemogenetic activation of astrocytes promotes remyelination and restores cognitive deficits in visceral hypersensitive rats
topic Biological sciences
Cognitive neuroscience
Neuroscience
url http://www.sciencedirect.com/science/article/pii/S2589004222021137
work_keys_str_mv AT mahadihasan chemogeneticactivationofastrocytespromotesremyelinationandrestorescognitivedeficitsinvisceralhypersensitiverats
AT zhuoguilei chemogeneticactivationofastrocytespromotesremyelinationandrestorescognitivedeficitsinvisceralhypersensitiverats
AT masturaakter chemogeneticactivationofastrocytespromotesremyelinationandrestorescognitivedeficitsinvisceralhypersensitiverats
AT zafariqbal chemogeneticactivationofastrocytespromotesremyelinationandrestorescognitivedeficitsinvisceralhypersensitiverats
AT faeeqausaila chemogeneticactivationofastrocytespromotesremyelinationandrestorescognitivedeficitsinvisceralhypersensitiverats
AT arunasurendranramkrishnan chemogeneticactivationofastrocytespromotesremyelinationandrestorescognitivedeficitsinvisceralhypersensitiverats
AT yingli chemogeneticactivationofastrocytespromotesremyelinationandrestorescognitivedeficitsinvisceralhypersensitiverats