# Experimental autoimmune encephalomyelitis pathogenesis alters along animal age: impact of S100B expression

## TL;DR

This study shows that age and the protein S100B influence the severity of a mouse model of multiple sclerosis, with S100B absence reducing disease markers across all ages.

## Contribution

The study reveals how S100B ablation mitigates MS-like disease progression in mice across different ages, including middle-aged animals.

## Key findings

- S100B absence reduced gliosis and inflammation in all age groups.
- Middle-aged mice showed increased regulatory T cells when S100B was absent.
- Older mice exhibited more severe disease with increased gliosis and impaired microglial activity.

## Abstract

Multiple Sclerosis (MS) is the leading inflammatory and non-traumatic cause of disability in young adults, with late-onset MS emerging in middle-aged patients often resulting in poorer treatment responses and worse prognoses. The calcium-binding protein S100B is elevated in MS patients, and its targeting has shown promise in reducing disease severity in experimental autoimmune encephalomyelitis (EAE) models. However, most studies on MS pathology have focused on young animal models, leaving a gap in understanding the effects of age and S100B ablation on disease progression throughout the lifespan. This study aimed to characterize EAE in mice of different ages, examining demyelination, inflammation, and immune responses to determine whether S100B ablation could mitigate MS pathogenesis across the lifespan. EAE was induced in six cohorts of C57BL/6 mice: young adults (3 months), older adults (6 months), and middle-aged (12 months), including corresponding S100B knockout (KO) groups, followed for 23 days. Upon sacrifice, spinal cords were assessed via immunohistochemistry and Real-Time qPCR, while splenocytes were analyzed for immune cell characterization. Results indicated a more severe disease course in 12-month-old mice, marked by increased gliosis, inflammation, and impaired microglial phagocytic activity. Notably, S100B absence reduced gliosis and inflammatory markers across all ages, with 12-month-old S100B KO mice showing increased regulatory T cells. These findings highlight the exacerbating role of age and elevated S100B in MS progression, underscoring the importance of identifying age-specific MS markers and therapeutic targets.

The online version contains supplementary material available at 10.1007/s11481-025-10195-5.