Inhibitory role of diazepam on autoimmune inflammation in rats with experimental autoimmune encephalomyelitis

M. J. Bibolini, N. L. Chanaday, N. S. Báez, A. L. Degano, C. G. Monferran, G. A. Roth

Research output: Contribution to journalArticle

Abstract

Glutamate and GABA are the main excitatory and inhibitory neurotransmitters in the CNS, and both may be involved in the neuronal dysfunction in neurodegenerative conditions. We have recently found that glutamate release was decreased in isolated synaptosomes from the rat cerebral cortex during the development of experimental autoimmune encephalomyelitis (EAE), the animal model of multiple sclerosis. In contrast to control animals where GABA induced a decrease in the evoked glutamate release, which was abolished by picrotoxin (a GABA A antagonist), synaptosomes from EAE rats showed a loss in the inhibition of the glutamate release mediated by GABA with a concomitant diminution of the flunitrazepam-sensitive GABA A receptor density. We have presently further evaluated the relevance of the GABAergic system in EAE by treating rats challenged for the disease with the GABA agonist diazepam. Administration of diazepam during 6 days starting at day 6 or 11 after EAE active induction led to a marked decrease of the disease incidence and histological signs associated with the disease. Cellular reactivity and antibody responses against the encephalitogenic myelin basic protein were also diminished. Beyond the effects of diazepam on the autoimmune, inflammatory response, we report also a positive effect on neurotransmission. Treatment with diazepam inhibited the previously described reduction in glutamate release in the frontal cortex synaptosomes from EAE animals. These data suggest that an endogenous inhibitory GABAergic system within the immune system is involved in the diazepam effect on EAE and indicate that increasing GABAergic activity potently ameliorates EAE.

Original languageEnglish (US)
Pages (from-to)421-428
Number of pages8
JournalNeuroscience
Volume199
DOIs
StatePublished - Dec 29 2011
Externally publishedYes

Keywords

  • Autoimmunity
  • Diazepam
  • GABAergic system
  • Multiple sclerosis
  • Neurotransmitter release

ASJC Scopus subject areas

  • Neuroscience(all)

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    Bibolini, M. J., Chanaday, N. L., Báez, N. S., Degano, A. L., Monferran, C. G., & Roth, G. A. (2011). Inhibitory role of diazepam on autoimmune inflammation in rats with experimental autoimmune encephalomyelitis. Neuroscience, 199, 421-428. https://doi.org/10.1016/j.neuroscience.2011.08.076