Microglia’s pathological pruning of synaptic structures in Parkinson’s Disease and L-DOPA induced dyskinesia models

FARES TAIE F.; RELA L.; BELFORTE J.; TARAVINI IRE.; PAFUNDO DE.; UNGER J.

Buenos Aires

Congreso; XXXVII Congreso Anual de la Sociedad Argentina de Investigación en Neurociencias.; 2022

Sociedad Argentina de Investigación en Neurociencias

Parkinsons disease results from the degeneration of mesencephalic dopaminergic neurons that innervate the striatum, a key structure for action selection and initiation. L-DOPA is the most effective treatment to restore the dopaminergic tone, however, it can lead to L-DOPA-induced dyskinesia (LID). Animal models show that the striatal dopaminergic denervation produces abnormal excitability and dendritic spine loss in striatal medium spiny neurons, that can be aggravated by L-DOPA. We will evaluate the role of microglia in such changes, both in the context of parkinsonism and LID. We hypothesize that activated microglial cells in parkinsonian and dyskinetic animals participate in the pathologic pruning of striatal synaptic structures. Doxycycline reduces microglial activation. We will evaluate its effect on plasticity of striatal neurons in mouse models of Parkinson’s disease and LID, through morphological analyses of single cells, immunohistochemistry and electrophysiological recordings, and correlations with behavior. We expect that inhibition of microglìa will prevent some of the plastic processes associated with Parkinsonism and dyskinesia. We also expect to reveal which plastic phenomena are compensatory or contribute to the pathology. If the results support our hypothesis, they will contribute to position microglia-mediated processes as potential therapeutic targets to treat the disease and/or LID.