Neurological Sciences

, Volume 31, Supplement 2, pp 255–259 | Cite as

Cognitive deficits in experimental autoimmune encephalomyelitis: neuroinflammation and synaptic degeneration

  • G. Mandolesi
  • G. Grasselli
  • G. Musumeci
  • Diego Centonze
Article

Abstract

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.

Keywords

EAE Synaptic alteration Microglia Excitotoxicity GABA interneurons 

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Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • G. Mandolesi
    • 1
  • G. Grasselli
    • 1
    • 2
  • G. Musumeci
    • 1
    • 2
  • Diego Centonze
    • 1
    • 2
  1. 1.Centro Europeo per la Ricerca sul Cervello (CERC)/Fondazione Santa LuciaRomeItaly
  2. 2.Neurologic Clinic, Department of NeuroscienceTor Vergata UniversityRomeItaly

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