Work

Short-term Exposure to Particulate Matter Triggers Selective Molecular and Behavioral Alterations in a Mouse Model of Multiple Sclerosis

Year: 2025

Type: article

Abstract: Multiple Sclerosis (MS) is a chronic disease of the Central Nervous System (CNS), where neuroinflammation and autoimmune response against myelin lead to functional impairments and psychiatric symptoms. Exposure to peaks of air pollution – and in particular of particulate matter (PM) - has been associated with increased hospitalizations for MS onset and relapses, pointing to persons with MS (or predisposed to develop MS) as a PM-vulnerable cohort. With the aim to disclose the biological substrate of such vulnerability, and to understand whether individuals primed to develop autoimmunity (as it occurs in MS and in the experimental autoimmune encephalomyelitis - EAE - animal model of MS) respond differently to PM, we firstly characterized plasmatic extracellular vesicles (EVs) and their microRNA (miRNA) cargo in healthy and presymptomatic EAE mice after exposure to PM10, compared to unexposed healthy and EAE mice. The response of EAE mice to PM10 did not differ in terms of EV number or source compared to that of healthy mice. Remarkable differences existed instead in the identity of deregulated EV-associated miRNAs, which in EAE mice were predicted to target several MS-relevant biological processes and nervous system-, immune- and inflammation- related pathways, possibly contributing to disease worsening. To validate our findings, we monitored EAE pathological course. PM10 exposure in the presymptomatic phase did not modify EAE course, as assessed by clinical and neuropathological analyses. Yet, in PM-exposed EAE mice we observed selective behavioral alterations - i.e. increased disinhibited, risk-taking and novelty-seeking behaviors - compatible with neurotransmitter imbalances linked with the detected EV-packaged miRNA deregulation. Overall, these data show a selective vulnerability of immunologically primed mice toward the effects of PM, detected at molecular and behavioral levels as early as in the pre-symptomatic stages of the pathology.

Source: European Journal of Histochemistry

DOI: 10.4081/ejh.2025.4482

Author: Neuroscience Rita Levi Montalcini

Institutions: Ospedale Koelliker, Neuroscience Institute Cavalieri Ottolenghi, University of Turin

Language: English

Topic: Multiple Sclerosis Research Studies

Subfield: Pathology and Forensic Medicine

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $1,024