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Synaptic alterations and immune response are sexually dimorphic in a non-pertussis toxin model of experimental autoimmune encephalomyelitis
Journal article   Open access   Peer reviewed

Synaptic alterations and immune response are sexually dimorphic in a non-pertussis toxin model of experimental autoimmune encephalomyelitis

Kayla L. Murphy, Roman Fischer, Kathryn A. Swanson, Ishaan J. Bhatt, Laura Oakley, Richard Smeyne, Valerie Bracchi-Ricard and John R. Bethea
Experimental neurology, v 323, 113061
Jan 2020
DOI: https://doi.org/10.1016/j.expneurol.2019.113061
PMID: 31499065
Featured in Collection :   UN Sustainable Development Goals @ Drexel
url
https://europepmc.org/articles/pmc6961843View
Accepted (AM)Open Access (License Unspecified),  Open

Abstract

Central nervous system Chronic neuropathic pain EAE Excitatory signaling Excitotoxicity Inflammation Leukocyte Multiple sclerosis Sex difference Synaptopathy
Multiple sclerosis is an autoimmune disorder of the central nervous system (CNS) characterized by locomotor impairments, cognitive deficits, affective disorders, and chronic pain. Females are predominately affected by MS compared to males and develop motor symptoms earlier. However, key symptoms affect all patients regardless of sex. Previous studies have shown that demyelination and axonal damage play key roles in symptom development, but it is unclear why sex differences exist in MS onset, and effective symptom treatment is still lacking. We here used a non-pertussis toxin (nPTX) experimental autoimmune encephalomyelitis (EAE) model in C57BL/6 mice, to explore chronic symptoms and sex differences in CNS autoimmunity. We observed that, like in humans, female mice developed motor disease earlier than males. Further, changes in pre- and post-synaptic protein expression levels were observed in a sexually dimorphic manner with an overall shift towards excitatory signaling. Our data suggest that this shift towards excitatory signaling is achieved through different mechanisms in males and females. Altogether, our study helps to better understand sex-specific disease mechanisms to ultimately develop better diagnostic and treatment tools. •nPTX EAE reflects some aspects female and male MS motor and sensory deficits.•Behavioral deficits are seen in both female and male EAE.•Macrophage-mediated innate immune response is stronger in males.•Synaptic protein expression are sexually dimorphic, but favor excitatory signaling.

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18 citations in Web of Science
17 citations in Scopus

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Collaboration types
Domestic collaboration
Web of Science research areas
Neurosciences
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