Brilliant Blue G, But Not Fenofibrate, Treatment Reverts Hemiparkinsonian Behavior and Restores Dopamine Levels in an Animal Model of Parkinson's Disease

Author(s)

Ferrazoli, Eneas G. ; de Souza, Hellio D. N. ; Nascimento, Isis C. ; Oliveira-Giacomelli, Agatha ; Schwindt, Telma T. ; Britto, Luiz R. ; Ulricht, Henning

• Document type: Journal article
• Source: CELL TRANSPLANTATION; v. 26, n. 4, p. 9-pg., 2017-01-01.

Abstract

Parkinson's disease (PD) is a neurodegenerative disorder, characterized by the loss of dopaminergic neurons in the substantia nigra and their projections to the striatum. Several processes have been described as potential inducers of the dopaminergic neuron death, such as inflammation, oxidative stress, and mitochondrial dysfunction. However, the death of dopaminergic neurons seems to be multifactorial, and its cause remains unclear. ATP-activating purinergic receptors influence various physiological functions in the CNS, including neurotransmission. Purinergic signaling is also involved in pathological scenarios, where ATP is extensively released and promotes sustained purinergic P2X7 receptor (P2X7R) activation and consequent induction of cell death. This effect occurs, among other factors, by oxidative stress and during the inflammatory response. On the other hand, peroxisome proliferator-activated receptor-gamma coactivator la (PGC-1 alpha) is involved in energy metabolism and mitochondrial biogenesis. Expression and activity upregulation of this protein has been related with reduction of oxidative stress and neuroprotection. Therefore, P2X7R and PGC-1 alpha are potential targets in the treatment of PD. Here hemiparkinsonism was induced by unilateral stereotactic injection of 6-OHDA in a rat model. After 7 days, the establishment of PD was confirmed and followed by treatment with the P2X7R antagonist Brilliant Blue G (BBG) or PGC-1 alpha agonist fenofibrate. BBG, but not fenofibrate, reverted hemiparkinsonian behavior accompanied by an increase in tyrosine hydroxylase immunoreactivity in the substantia nigra. Our results suggest that the P2X7R may be a therapeutic target in Parkinson's disease. (AU)

• FAPESP's process: 12/20685-5 - Role of kinins receptor B2 in therapy of Parkinson's Disease in animal model.
• Grantee: Héllio Danny Nóbrega de Souza
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 15/18730-0 - Lung cancer stem cells by DNA aptamers identification / purification and kallikrein-kinin system study on tumor progression
• Grantee: Isis Cristina Corrêa Do Nascimento
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 11/09852-4 - CELL THERAPY COMBINED TO P2X7R BLOCKING AND PGC-1± ACTIVATION IN A RAT MODEL FOR PARKINSON DISEASE.
• Grantee: Enéas Galdini Ferrazoli
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 12/50880-4 - Stem cells: from basic studies of kinin and purinergic receptor roles towards therapeutical applications
• Grantee: Alexander Henning Ulrich
• Support Opportunities: Research Projects - Thematic Grants