Cognitive deficits in experimental autoimmune encephalomyelitis: neuroinflammation and synaptic degeneration
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Multiple sclerosis (MS) is characterized by auto-reactive T cells that respond to central nervous system (CNS)-based antigens and affect motor, sensory as well as behavioral and cognitive functions. Cognitive deficits are now considered an early manifestation of the disease in MS patients. However, the pathophysiology responsible for the cognitive symptoms in MS remains unclear. Increasing evidence from a mouse model of MS, the experimental autoimmune encephalomyelitis (EAE), suggests a correlation between the synaptopathy induced by microglia activation in the early phase of the disease and cognitive dysfunction. In particular, EAE causes deficits in hippocampal-dependent learning and memory that are associated with early microglial activation, synaptic loss and neurodegeneration. Interestingly, inflammatory cytokines released from infiltrating lymphocytes or activated microglia are able to alter synaptic transmission. Increased glutamate-mediated transmission and loss of GABAergic inputs were observed in EAE. They may thus underlie cognitive dysfunction in this model and in MS.
KeywordsEAE Synaptic alteration Microglia Excitotoxicity GABA interneurons
Conflict of interest statement
The authors declare that they have no conflict of interest related to the publication of this article.
- 2.Centonze D, Muzio L, Rossi S, Furlan R, Bernardi G, Martino G (2009) The link between inflammation, synaptic transmission and neurodegeneration in multiple sclerosis. Cell Death Differ. doi: 10.1038/cdd.2009.179
- 6.Kim J, Basak JM, Holtzman DM (2009) The role of apolipoprotein E in Alzheimer’s disease. Neuron 29(48):15317–15322Google Scholar
- 8.Ziehn MO, Avedisian AA, Tiwari-Woodruff S, Voskuhl RR (2010) Hippocampal CA1 atrophy and synaptic loss during experimental autoimmune encephalomyelitis, EAE. Lab Invest. doi: 10.1038/labinvest.2010.6
- 14.Centonze D, Muzio L, Rossi S, Cavasinni F, De Chiara V, Bergami A, Musella A, D’Amelio M, Cavallucci V, Martorana A, Bergamaschi A, Cencioni MT, Diamantini A, Butti E, Comi G, Bernardi G, Cecconi F, Battistini L, Furlan R, Martino G (2009) Inflammation triggers synaptic alteration and degeneration in experimental autoimmune encephalomyelitis. J Neurosci 29:3442–3452CrossRefPubMedGoogle Scholar
- 17.Morellini F, Sivukhina E, Stoenica L, Oulianova E, Bukalo O, Jakovcevski I, Dityatev A, Irintchev A, Schachner M (2010) Improved reversal learning and working memory and enhanced reactivity to novelty in mice with enhanced GABAergic innervation in the dentate gyrus. Cereb Cortex. doi: 10.1093/cercor/bhq017