Strain and sex differences in somatosensation and sociability during experimental autoimmune encephalomyelitis

Abstract

Multiple Sclerosis (MS) is an immune-mediated disease that results in major locomotor deficits. However, recent studies have revealed that fatigue, slow processing speed, and memory impairment are the top variables impacting employment status for MS patients. These suggest that cognitive effects may have a greater impact on productivity, lifestyle, and quality of life than do disease-related motor deficits. However, these debilitating non-locomotive effects have been largely overlooked in rodent models of the disease, such as experimental autoimmune encephalomyelitis (EAE). We hypothesized that murine EAE can also be used to assess non-locomotive dysfunctions (mood, sociability, muscle strength, and balance), as well as potential biases in these dysfunctions due to sex and/or strain. We actively immunized male and female C57BL/6 (B6) and SJL mice for EAE and evaluated their performance on the Deacon's weight grip test, Kondziela's inverted screen test, Hall's rope grip test, manual von Frey test for somatic nociception, and a three-chamber social preference paradigm. We hypothesized that EAE progression is associated with changes in muscle strength, balance, pain, and sociability and that these variations are linked to sex and/or strain. Our results indicate that strain but not sex influenced differences in muscle strength and balance during EAE, and both sex and strain have an impact on mechanical nociception, regardless of EAE disease status. Furthermore, both sex and strain had complex effects on differences in sociability. In conclusion, testing these additional modalities during EAE helps to unveil other signs and symptoms that could be used to determine the efficacy of a drug or treatment in the modulation of a MS-like behavior.

Thermoregulatory dynamics reveal sex-specific inflammatory responses to experimental autoimmune encephalomyelitis in mice: Implications for multiple sclerosis-induced fatigue in females

“…The C57BL/6 model of EAE generates a characteristic acute monophasic profile and stable chronic disease course ( Berard et al, 2010 ). However, despite the clear female-biased differences in MS incidence and outcome, the C57BL/6 females' preponderance in EAE susceptibility is still controversial ( Hoghooghi et al, 2020 ; Ondek et al, 2021 ; Papenfuss et al, 2004 ). In the present study, we observed a sexual dimorphism in C57BL/6 mice with respect to disease outcomes.…”

Thermoregulatory Dynamics Reveal Sex-Specific Inflammatory Responses to Experimental Autoimmune Encephalomyelitis in Mice: Implications for Multiple Sclerosis-Induced Fatigue in Females

“…The C57BL/6 model of EAE generates a characteristic acute monophasic profile and stable chronic disease course (Berard et al, 2010). However, despite the clear female-biased differences in MS incidence and outcome, the C57BL/6 females’ preponderance in EAE susceptibility is still controversial (Hoghooghi et al, 2020; Ondek, Nasirishargh, Dayton, Nuño, & Cruz-Orengo, 2021; Papenfuss et al, 2004). In the present study, we observed a sexual dimorphism in C57BL/6 mice with respect to disease outcomes.…”