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Updated: Jan 4, 2026
Comprehensive Autopsy Program for Individuals with Multiple Sclerosis
Published on: July 19, 2019
MicroRNA profiles of MS gray matter lesions identify modulators of the synaptic protein synaptotagmin-7
Lena Fritsche1, Sarah Teuber-Hanselmann1, Daniel Soub1
1Institute of Neuropathology, University Hospital Essen, D-45147, Essen, Germany.
Abstract:
We established microRNA (miRNA) profiles in gray and white matter multiple sclerosis (MS) lesions and identified seven miRNAs which were significantly more upregulated in the gray matter lesions. Five of those seven miRNAs, miR-330-3p, miR-4286, miR-4488, let-7e-5p, miR-432-5p shared the common target synaptotagmin7 (Syt7). Immunohistochemistry and transcript analyses using nanostring technology revealed a maldistribution of Syt7, with Syt7 accumulation in neuronal soma and decreased expression in axonal structures. This maldistribution could be at least partially explained by an axonal Syt7 transport disturbance. Since Syt7 is a synapse-associated molecule, this maldistribution could result in impairment of neuronal functions in MS patients. Thus, our results lead to the hypothesis that the overexpression of these five miRNAs in gray matter lesions is a cellular mechanism to reduce further endogenous neuronal Syt7 production. Therefore, miRNAs seem to play an important role as modulators of neuronal structures in MS.
Insights
MicroRNAs (miRNAs) are upregulated in gray matter lesions of multiple sclerosis (MS). This may impair neuronal function by disrupting synaptotagmin7 (Syt7) transport and expression in MS patients.
Area of Science:
- Neuroscience
- Molecular Biology
- Genetics
Background:
- Multiple sclerosis (MS) is a demyelinating disease affecting both gray and white matter.
- Neuronal dysfunction in gray matter lesions is a key factor in MS pathogenesis.
- MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression.
Purpose of the Study:
- To investigate miRNA expression profiles in gray and white matter MS lesions.
- To identify specific miRNAs and their targets involved in gray matter pathology in MS.
- To elucidate the role of miRNAs in neuronal dysfunction in MS.
Main Methods:
- Comparative analysis of miRNA expression in gray and white matter MS lesions.
- Identification of common miRNA targets using bioinformatics and transcript analysis.
- Immunohistochemistry and Nanostring technology for protein and transcript expression analysis.
- Assessment of synaptotagmin7 (Syt7) distribution in neuronal structures.
Main Results:
- Seven miRNAs were significantly upregulated in gray matter MS lesions compared to white matter lesions.
- Five specific miRNAs (miR-330-3p, miR-4286, miR-4488, let-7e-5p, miR-432-5p) share synaptotagmin7 (Syt7) as a common target.
- Syt7 exhibited abnormal distribution in neurons, with accumulation in soma and reduced expression in axons, suggesting impaired axonal transport.
- This Syt7 maldistribution may lead to synaptic dysfunction and neuronal impairment in MS.
Conclusions:
- Upregulation of specific miRNAs in gray matter MS lesions may represent a cellular mechanism to downregulate Syt7.
- MiRNAs play a crucial role in modulating neuronal structures and function in the context of MS.
- Disruption of Syt7 transport and expression by miRNAs contributes to neurodegeneration in MS gray matter.
