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Migraine and major depression: localizing shared genetic susceptibility in different cell types of the nervous systems

Authors :
X. Michelle Androulakis
Xuanxuan Yu
Xia Zhu
Melinda A. Thiam
Guoshuai Cai
Source :
Frontiers in Neurology, Vol 14 (2023)
Publication Year :
2023
Publisher :
Frontiers Media S.A., 2023.

Abstract

BackgroundThere is a bidirectional relationship between migraine and major depression disorder (MDD). They likely share important risk genes associated with different cell types in the central nervous system (CNS) and peripheral nervous system (PNS). Profiling the expression of these genes in specific cell types is critical in understanding the pathophysiology of the relationship between migraine and MDD.MethodsAssociated genes shared by migraine and MDD were identified by consolidating multiple curations of human disease-gene associations. Subsequently, the expression of overlapping genes was profiled and compared across the different cell types in CNS, PNS and neurovascular cells using eight single cell RNA sequencing datasets, including two human CNS datasets, two mouse CNS datasets, one human PNS dataset and three mouse PNS datasets.Results45 shared genes between migraine and MDD were identified. Consistently found in all eight datasets, dopaminergic and serotonergic neurotransmitters were broadly expressed in CNS and PNS cell types. Glutamatergic and endocannabinoid genes were specifically expressed in CNS neurons and astrocytes. Synthesis and/or Release and Binding of Neuropeptides were specifically expressed in PNS peptidergic nociceptor (PEP). Genes related to inflammatory factors and immune responses were specifically expressed in CNS microglia. Among which, IL1B and COMT were highly expressed in CNS microglia cells.ConclusionSingle cell RNA sequencing of the CNS and PNS helps to identify the shared genes between migraine and MDD that are enriched in specific cell types. The findings provide new insight in understanding the underlying mechanism of action for the bidirectional co-morbidity between migraine and MDD.

Details

Language :
English
ISSN :
16642295
Volume :
14
Database :
Directory of Open Access Journals
Journal :
Frontiers in Neurology
Publication Type :
Academic Journal
Accession number :
edsdoj.40f151f4b76a45a2a76b5ef7f582ad67
Document Type :
article
Full Text :
https://doi.org/10.3389/fneur.2023.1254290