Navegando por Palavras-chave "Brilliant Blue G (BBG)"

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    Brilliant Blue G, But Not Fenofibrate, Treatment Reverts Hemiparkinsonian Behavior and Restores Dopamine Levels in an Animal Model of Parkinson's Disease
    (Cognizant Communication Corp, 2017) Ferrazoli, Eneas Galdini [UNIFESP]; de Souza, Hellio D. N.; Nascimento, Isis C.; Oliveira-Giacomelli, Agatha; Schwindt, Telma T.; Britto, Luiz R.; Ulricht, Henning
    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.
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    O receptor P2X7 e a via de PGC-1A/PPAR como alvos na estratégia do desenvolvimento de terapias para a doença de Parkinson
    (Universidade Federal de São Paulo (UNIFESP), 2017-08-08) Ferrazoli, Enéas Galdini [UNIFESP]; Ulrich, Alexander Henning [UNIFESP]; Gomes, Telma Tiemi Schwindt Diniz [UNIFESP]; http://lattes.cnpq.br/8780348666074054; http://lattes.cnpq.br/9571481236686866; http://lattes.cnpq.br/7508889777108883; Universidade Federal de São Paulo (UNIFESP)
    Parkinson's Disease (PD) is characterized by the loss of dopaminergic neurons in the substantia nigra and their projections to the striatum, and there are no therapies that significantly delay its progression so far. Currently, the most common treatment for PD is the administration of Levodopa, but this drug has limited efficacy and many side effects, such as dyskinesias. Recently, several groups have demonstrated the participation of purinergic receptors, especially the P2X7 receptor (P2X7R), and the peroxisome proliferator activated receptor (PPAR), in neuroinflammatory and neurodegenerative pathways, suggesting that these might be important targets for therapies for neurodegenerative diseases. It is also known that the inflammation process is closely linked to the mechanisms of neuronal death in PD. Further, neural stem / progenitor cells express various chemokines and chemokine receptors that are involved in the homing of these cells to sites of injury in the central nervous system; thus transplantation of neural stem / progenitor cells is indicated as a promising strategy for the treatment of neurodegenerative diseases. The objective of the present study was to evaluate the therapeutic effect of the use of the P2X7R blocker Brilliant Blue G, the PPAR activator fenofibrate, and neural progenitor cell transplantation in an in vitro model for PD. For this purpose, we used the hemiparkinsonism model induced by 6-hydroxy-dopamine. The apomorphine-induced rotational behavior, characteristic of this model, and histological analysis of tyrosine hydroxylase expression were used as parameters to determine the effects of the used treatments. The obtained results obtained show that the blockade of P2X7R by BBG induced a significant decrease of apomorphine-evoked rotations and the recovery of dopaminergic neurons in the substantia nigra. However, treatments with fenofibrate and neural progenitor cells did not promote any improvement compared to animals treated with saline. In summary, we can conclude that P2X7R may be an important therapeutic target in Parkinson's disease.