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Updated: Jul 15, 2025
Rat Model of Widespread Cerebral Cortical Demyelination Induced by an Intracerebral Injection of Pro-Inflammatory Cytokines
Published on: September 21, 2021
Carnosine synthase deficiency aggravates neuroinflammation in multiple sclerosis
Jan Spaas1, Thibaux Van der Stede2, Sarah de Jager3
1University MS Center (UMSC), Hasselt - Pelt, Belgium; BIOMED Biomedical Research Institute, Faculty of Medicine and Life Sciences, Hasselt University, Diepenbeek, Belgium; Department of Movement and Sports Sciences, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium.
Loss of carnosine synthase (CARNS1) in multiple sclerosis (MS) lesions worsens neuroinflammation and disease severity. Endogenous carnosine protects against MS-related damage, but CARNS1 is not essential for remyelination.
Area of Science:
- Neuroimmunology
- Neurobiology
- Demyelinating Diseases
Background:
- Multiple sclerosis (MS) involves autoimmune neuroinflammation, demyelination, and failed remyelination.
- Carnosine, a histidine-containing dipeptide (HCD), shows promise in animal models of MS.
- The role of endogenous carnosine in MS pathology remains unclear.
Purpose of the Study:
- To investigate the role of carnosine synthase (CARNS1), the enzyme synthesizing carnosine, in MS.
- To determine if endogenous carnosine protects against MS-related neuroinflammation, demyelination, and remyelination failure.
Main Methods:
- Studied CARNS1 expression in human MS lesions and EAE/cuprizone mouse models.
- Utilized Carns1-knockout (KO) mice lacking endogenous HCDs in the EAE model.
- Assessed neuroinflammation, clinical symptoms, and remyelination in mouse models.
Main Results:
- CARNS1 expression decreased in demyelinated MS lesions and mouse models but returned upon remyelination.
- Carns1-KO mice exhibited exacerbated neuroinflammation and clinical symptoms in EAE, partially improved by exogenous carnosine.
- Impaired acrolein clearance in Carns1-KO mice may drive disease worsening, suggesting a central mechanism.
- CARNS1 is not required for oligodendrocyte differentiation or remyelination; HCDs did not prevent cuprizone-induced demyelination.
Conclusions:
- Loss of CARNS1 in demyelinated MS lesions exacerbates disease by reducing endogenous protection against neuroinflammation.
- Endogenous carnosine plays a protective role against MS-related neuroinflammation and clinical worsening.
- CARNS1's protective effect seems independent of oligodendrocyte differentiation and direct impact on cuprizone-induced demyelination.
