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2015-05-22 - Colloque/Présentation - communication orale - Anglais - 1 page(s)

Rinchon Adeline , Brunois Célestine, Villers Agnès , Ris Laurence , "Hippocampal synaptic plasticity and neuroinflammation during the course of experimental autoimmune encephalomyelitis" in 11th National Congress of the Belgian Society for Neuroscience , Mons, Belgique, 2015

  • Codes CREF : Neurophysiologie (DI3224)
  • Unités de recherche UMONS : Neurosciences (M119)
  • Instituts UMONS : Institut des Sciences et Technologies de la Santé (Santé), Institut des Biosciences (Biosciences)
Texte intégral :

Abstract(s) :

(Anglais) Hippocampal synaptic plasticity and neuroinflammation during the course of experimental autoimmune encephalomyelitis Synaptic plasticity is the ability of neurons to modulate the strength of their synaptic transmission in relation to electrical activity. This process enables to modify neural circuits dynamic and ensures memory consolidation in the hippocampus. Although the immune system has primarily an essential neuroprotective role in the brain, it is also physiologically implicated in the remodeling of synaptic circuits. Innate and peripheral immune cells play a key role in modulating learning, memory and neural plasticity (Yirmiya and Goshen, 2011). A complex crosstalk takes place between neurons, microglia, astrocytes and infiltrating immune cells to promote structural and functional changes in neuronal networks. More specifically, glial cells are considered as the third element of synapses contributing to neurotransmission and several forms of synaptic plasticity like long-term potentiation (LTP). However, this system can be rapidly disrupted in inflammatory conditions and can alter neuronal networks functioning leading to cognitive impairments. Secreted inflammatory mediators can disturb the neurophysiological actions of immune processes and generate deleterious effects on memory (Di Filippo et al., 2008). Cognitive impairments are very common in inflammatory disorders but the mechanisms responsible of these deficits are still poorly understood. Immune responses are complex, being either neuroprotective or detrimental, and largely depending on the stimulus, the context, the duration of the inflammatory process and the type of activated inflammatory cells. With this view, this project aims to study the impact of neuroinflammation on neuronal network activity and synaptic plasticity into the hippocampus in order to highlight the molecular and cellular inflammatory actors responsible of cognitive disorders. Our work is based on a model of CNS chronic inflammatory disease, EAE (experimental autoimmune encephalomyelitis). EAE develops with a relapsing-remitting course allowing to partly restore motor performances with disease progression. Our analyses were realized during the peak of the disease and the remission stage in male and female mice. The evolution of the activation of glial cells was followed in the hippocampus during the disease course through fluorescent immunostaining of astrocytes and microglia with the biomarkers GFAP and Iba1 respectively. In male EAE mice, the number of both activated microglia and astrocytes follows the disease progression as it enhances at the peak and then decreases during the remission stage. A more important reduction of activated glial cells was also observed during the long remission stage compared to the short one. This evolution is nevertheless more pronounced for microglial cells than for astrocytes. In female EAE mice, the same results were observed but the distinction between the short and the long remission stage is not so evident. Moreover, the comparison of inflammatory state in the hippocampus of male and female mice revealed a higher baseline inflammatory level in female mice. Hippocampal synaptic plasticity was analyzed during the course of EAE by LTP measurements at the level of synapses between the Schaffer’s collaterals and the CA1 region of hippocampal slices from male and female mice using ex vivo electrophysiological recordings. Similar results were obtained from male and female experiments and showed a higher level of potentiation at the peak of the disease compared to the control situation. More interestingly, the LTP was reduced to the control level during the remission stage and it continues to decrease when the remission is longer extended to reach a level significatively lower than the control one suggesting a time dependent impairment of hippocampal plastic potential during the EAE remission stage. By using a behavioral test based on the fear conditionning, no alteration in the learning abilities of remitting mice was detected but a memory deficit was revealed by a lower freezing level compared to controls 24h after the learning episode. In conclusion, our study demonstrated a developing inflammatory state in the hippocampus of mice during EAE along with modifications of synaptic plasticity. More interestingly, we detected a cognitive impairment in EAE mice during the long remission stage that is conversely correlated to motor performances. Although hippocampal inflammatory state decreases and motor disturbances improve, the cognitive state of these mice gradually declines. A better understanding of inflammatory mechanisms causing structural and functional impairments in the hippocampus could contribute to the design of new therapeutic strategies to improve cognitive performances of patients with inflammatory disorders.