Proceedings of The Physiological Society

Europhysiology 2018 (London, UK) (2018) Proc Physiol Soc 41, PCB300

Poster Communications

Dopamine and glutamate dysbalance in the dorsal striatum of parkinsonian mice: glial cells induced inflammatory environment

M. Pereira-dos-Santos1, G. H. Dias-de-Abreu1, J. Rocca2, S. Hamadat2, J. Sepúlveda-Diaz2, P. Michel2, R. Raisman-Vozari2, E. -. Del-Bel1

1. MFPB- Physiology, University of Sao Paulo-FORP, Ribeirao Preto, Sao Paulo, Brazil. 2. ICM - Institut du Cerveau et de la Moelle épinière, Paris, France.

L-DOPA-induced dyskinesia (LID) is associated to a pro-inflammatory environment with the contribution of glial cells (astrocytes and microglia) in the dopamine-denervated striatum. This setting results from a combination of dopamine (DA) accumulation following L-DOPA reposition and abnormal glutamate (GLU) release from motor cortex. Our aim was to determine in vivoin the lesioned striatum and in vitroin purified cultured glial cells whether the response to increased DA and GLU in composition with activation of glial cells would influence LID and the production of inflammatory cytokines. C57BL/6 6-hydroxydopamine-lesioned mice received L-DOPA (25 mg/kg + Benserazide 10 mg/kg i.p.) for twenty-one days and had their striatum analyzed by immunohistochemistry. Primary glial cells culture preparation was performed based on an established protocol and stimulated with L-DOPA, DA or GLU. In the DA-denervated dorsal striatum of dyskinetic mice there was an augmentation of the cytokines TNF-α, IL-1β and IL-6, astrocytic activation and an increase of reactive microglia. Cultured primary astrocytes stimulated by L-DOPA and DA (3 and 10 µM) presented reduced TNF-α and IL-6 levels; GLU (50 and 500 µM) increased GFAP expression and TNF-α production. In cultured microglial cells, DA diminished Iba-1 expression, whereas GLU induced Iba-1 increase. The combination of anti-inflammatory compounds capsazepine/cannabidiol (5 mg/kg + 30 mg/kg i.p.) attenuated LID. This effect was, at least in part, via inhibition of the pro-inflammatory cytokine TNF-αproduction.We concluded that glial activation accompanies cytokine production in striatum of dyskinetic mice, and an imbalance of GLU and DA might contribute to this inflammatory environment.

Where applicable, experiments conform with Society ethical requirements