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Synapsin I deletion reduces neuronal damage and ameliorates clinical progression of experimental autoimmune encephalomyelitis
- Source :
- Brain, Behavior, and Immunity. 68:197-210
- Publication Year :
- 2018
- Publisher :
- Elsevier BV, 2018.
-
Abstract
- The classical view of multiple sclerosis (MS) pathogenesis states that inflammation-mediated demyelination is responsible for neuronal damage and loss. However, recent findings show that impairment of neuronal functions and demyelination can be independent events, suggesting the coexistence of other pathogenic mechanisms. Due to the inflammatory milieu, subtle alterations in synaptic function occur, which are probably at the basis of the early cognitive decline that often precedes the neurodegenerative phases in MS patients. In particular, it has been reported that inflammation enhances excitatory synaptic transmission while it decreases GABAergic transmission in vitro and ex vivo. This evidence points to the idea that an excitation/inhibition imbalance occurs in the inflamed MS brain, even though the exact molecular mechanisms leading to this synaptic dysfunction are as yet not completely clear. Along this line, we observed that acute treatment of primary hippocampal neurons in culture with pro-inflammatory cytokines leads to an increased phosphorylation of synapsin I (SynI) by ERK1/2 kinase and to an increase in the frequency of spontaneous synaptic vesicle release events, which is prevented by SynI deletion. In vivo, the ablation of SynI expression is protective in terms of disease progression and neuronal damage in the experimental autoimmune encephalomyelitis mouse model of MS. Our results point to a possible key role in MS pathogenesis of the neuronal protein SynI, a regulator of excitation/inhibition balance in neuronal networks.
- Subjects :
- 0301 basic medicine
Synapsin I
Encephalomyelitis, Autoimmune, Experimental
MAP Kinase Signaling System
Immunology
Biology
Hippocampus
Synaptic vesicle
Endocrine and Autonomic System
Multiple sclerosis
Synapse
Mice
03 medical and health sciences
Behavioral Neuroscience
0302 clinical medicine
medicine
Animals
Multiple sclerosi
Phosphorylation
Cognitive decline
Cytokine
Inflammation
Mice, Knockout
Neurons
Endocrine and Autonomic Systems
Experimental autoimmune encephalomyelitis
Brain
Synapsin
Neuron
Synapsins
medicine.disease
Mice, Inbred C57BL
Disease Models, Animal
Neuroprotective Agents
030104 developmental biology
medicine.anatomical_structure
Synapses
Disease Progression
Cytokines
Synaptic Vesicles
Neuroscience
030217 neurology & neurosurgery
Subjects
Details
- ISSN :
- 08891591
- Volume :
- 68
- Database :
- OpenAIRE
- Journal :
- Brain, Behavior, and Immunity
- Accession number :
- edsair.doi.dedup.....5bfaa9b750d1dd615e8c73d6877f7aa5