Multiple sclerosis: what have we learned and can we still learn from electron microscopy

Area of Science:

• Neuroscience
• Pathology
• Biotechnology

Background:

• Multiple sclerosis (MS) is an inflammatory neurodegenerative disease characterized by demyelination in the central nervous system.
• While remyelination can occur, it becomes less effective as MS progresses, and even normal-appearing brain tissue shows alterations.
• Current understanding of MS molecular pathogenesis, lesion formation, and demyelination is limited despite various analytical methods.

Purpose of the Study:

• To review the pathogenesis of MS and its ultrastructural features.
• To highlight the potential of advanced electron microscopy (EM) techniques in understanding MS pathology.
• To explore how EM can provide new insights into lesion formation, remyelination failure, and diffuse pathology for therapeutic development.

Main Methods:

• Review of existing literature on MS pathogenesis and ultrastructural features.
• Discussion of the capabilities of advanced electron microscopy (EM) for high-resolution structural analysis.
• Integration of potential EM findings with immunohistochemistry and 'omics' data.

Main Results:

• MS pathology differs between grey and white matter lesions and their normal-appearing counterparts due to distinct cellular compositions.
• Advanced EM offers nanometre-scale resolution, surpassing previous studies and enabling detailed structural analysis.
• EM can potentially elucidate molecular mechanisms underlying MS lesion development, impaired remyelination, and diffuse pathology.

Conclusions:

• Cutting-edge EM techniques hold significant promise for uncovering novel insights into the ultrastructural basis of MS.
• Understanding these detailed pathological processes through EM may facilitate the development of new therapeutic strategies for multiple sclerosis.
• Further exploration using advanced EM is crucial for a comprehensive understanding of MS pathogenesis.