l-DOPA-induced dyskinesia in Parkinson's disease: Are neuroinflammation and astrocytes key elements?
Inflammation in Parkinson's disease (PD) is a new concept that has gained ground due to the potential of mitigating dopaminergic neuron death by decreasing inflammation. The solution to this question is likely to be complex. We propose here that the significance of inflammation in PD may go beyond the nigral cell death. The pathological process that underlies PD requires years to reach its full extent. A growing body of evidence has been accumulated on the presence of multiple inflammatory signs in the brain of PD patients even in very late stages of the disease. Because neuron-microglia-astrocyte interactions play a major role in the plasticity of neuronal response to l-DOPA in post-synaptic neurons, we focused this review on our recent results of l-DOPA-induced dyskinesia in rodents correlating it to significant findings regarding glial cells and neuroinflammation. We showed that in the rat model of PD/l-DOPA-induced dyskinesia there was an increased expression of inflammatory markers, such as the enzymes COX2 in neurons and iNOS in glial cells, in the dopamine-denervated striatum. The gliosis commonly seem in PD was associated with modifications in astrocytes and microglia that occur after chronic treatment with l-DOPA. Either as a cause, consequence, or promoter of progression of neuronal degeneration, inflammation plays a role in PD. The key aims of current PD research ought to be to elucidate (a) the time sequence in which the inflammatory factors act in PD patient brain and (b) the mechanisms by which neuroinflammatory response contributes to the collateral effects of l-DOPA treatment.
Department of MFPB-Physiology, FORP, Campus USP, University of São Paulo, Av. Café, s/no, Ribeirão Preto, SP, 14040-904, Brazil. eadelbel@forp.usp.br.|Center for Interdisciplinary Research on Applied Neurosciences (NAPNA), São Paulo, Brazil. eadelbel@forp.usp.br.|Department of Physiology, FMRP, São Paulo, Brazil. eadelbel@forp.usp.br.|Department of Neurology and Behavioral Neuroscience, FMRP, Campus USP, University of São Paulo, Av. Bandeirantes 13400, Ribeirão Preto, SP, 14049-900, Brazil. eadelbel@forp.usp.br.
Elaine
E
Del-Bel
Department of MFPB-Physiology, FORP, Campus USP, University of São Paulo, Av. Café, s/no, Ribeirão Preto, SP, 14040-904, Brazil.|Center for Interdisciplinary Research on Applied Neurosciences (NAPNA), São Paulo, Brazil.
Mariza
M
Bortolanza
Department of MFPB-Physiology, FORP, Campus USP, University of São Paulo, Av. Café, s/no, Ribeirão Preto, SP, 14040-904, Brazil.|Center for Interdisciplinary Research on Applied Neurosciences (NAPNA), São Paulo, Brazil.|Department of Physiology, FMRP, São Paulo, Brazil.
Maurício
M
Dos-Santos-Pereira
Department of MFPB-Physiology, FORP, Campus USP, University of São Paulo, Av. Café, s/no, Ribeirão Preto, SP, 14040-904, Brazil.|Center for Interdisciplinary Research on Applied Neurosciences (NAPNA), São Paulo, Brazil.|Department of Neurology and Behavioral Neuroscience, FMRP, Campus USP, University of São Paulo, Av. Bandeirantes 13400, Ribeirão Preto, SP, 14049-900, Brazil.
Keila
K
Bariotto
INSERM UMR 1127, CNRS UMR 7225, UPMC, Thérapeutique Expérimentale de la Neurodégénérescence, Hôpital de la Salpetrière-ICM (Institut du cerveau et de la moelle épinière), Paris, France.
Rita
R
Raisman-Vozari
D000818:Animals; D000978:Antiparkinson Agents / Q000009:adverse effects* / Q000627:therapeutic use; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D004409:Dyskinesia, Drug-Induced / Q000209:etiology / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D007980:Levodopa / Q000009:adverse effects* / Q000627:therapeutic use; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D010300:Parkinson Disease / Q000188:drug therapy* / Q000378:metabolism
D000978:Antiparkinson Agents; D007980:Levodopa
COX2; dorsal striatum; glial cells; neuroprotection; nitric oxide