HYPOTHESIS AND THEORY article
Front. Neurol.
Sec. Multiple Sclerosis and Neuroimmunology
Volume 16 - 2025 | doi: 10.3389/fneur.2025.1653134
This article is part of the Research TopicThe Role of Neurotransmitters: From Normal Aging to Age-Related Diseases, Volume IIView all articles
System-Level Hypothesis of Dopamine Imbalance in Early Multiple Sclerosis
Provisionally accepted
- 1National Research Council (CNR), Roma, Italy
- 2Istituto di Scienze e Tecnologie della Cognizione Consiglio Nazionale delle Ricerche, Rome, Italy
- 3Universita degli Studi di Roma La Sapienza, Rome, Italy
- 4Universita degli Studi di Genova Dipartimento di Neuroscienze Riabilitazione Oftalmologia Genetica e Scienze Materno-Infantili, Genoa, Italy
Select one of your emails
You have multiple emails registered with Frontiers:
Notify me on publication
Please enter your email address:
If you already have an account, please login
You don't have a Frontiers account ? You can register here
Multiple Sclerosis (MS) is a chronic autoimmune disorder of the central nervous system, with evidence suggesting that age-related brain changes may influence its progression. Clinically Isolated Syndrome (CIS) often marks an early phase of MS, with optic neuritis frequently presenting as a symptom. Despite recognition as an early indicator, the mechanisms driving optic neuritis and its contribution to MS progression remain unclear. Traditionally, immunemediated inflammation has dominated MS research; however, emerging evidence highlights neurotransmitter dysregulation-especially involving dopamine-as a crucial factor in disease pathophysiology. The impact of dopamine imbalance on neural circuits and its role in advancing MS requires further investigation. This paper proposes a system-level, dopamine-based hypothesis to explain MS origins, focusing on early stages in CIS. Building on a review of recent literature linking dopaminergic dysfunction, neuroinflammation, and demyelination, the model suggests that optic nerve demyelination, as seen in optic neuritis, disrupts dopamine signaling, triggering a cascade of neural alterations that drive MS pathogenesis. By emphasizing dopamine role in CIS and early MS, this framework offers a novel perspective on the neurobiological mechanisms underlying the disease. This approach complements current research on neurotransmitter involvement in age-related conditions, expanding understanding of how neurotransmitter imbalances may influence MS and related disorders.
Keywords: clinically isolated syndrome, demyelination, Dopamine dysregulation, Multiple Sclerosis, network neuroscience, neurodegeneration, Neurotransmitter imbalance, Optic Neuritis
Received: 25 Jun 2025; Accepted: 08 Sep 2025.
Copyright: © 2025 Caligiore, Schirripa and Biggio. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Daniele Caligiore, National Research Council (CNR), Roma, Italy
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.