Navegando por Palavras-chave "Fenofibrate"

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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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    Neuroprotective effects of peroxisome proliferator-activated receptor alpha and gamma agonists in model of parkinsonism induced by intranigral 1-methyl-4-phenyl-1,2,3,6-tetrahyropyridine
    (Elsevier B.V., 2014-11-01) Barbiero, Janaina K.; Santiago, Ronise M.; Persike, Daniele Suzete [UNIFESP]; Silva Fernandes, Maria Jose da [UNIFESP]; Tonin, Fernanda S.; Cunha, Claudio da; Boschen, Suelen Lucio; Lima, Marcelo M. S.; Vital, Maria A. B. F.; Univ Fed Parana; Universidade Federal de São Paulo (UNIFESP)
    A large body of evidence suggests that peroxisome proliferator-activated receptor (PPAR) agonists may improve some of the pathological features of Parkinson's disease (PD). in the present study, we evaluated the effects of the PPAR-alpha agonist fenofibrate (100 mg/kg) and PPAR-gamma agonist pioglitazone (30 mg/kg) in a rat model of parkinsonism induced by intranigral 1-methyl-4-phenyl-1,2,3,6-tetrahyropyridine (MPTP). Male Wistar rats were pretreated with both drugs for 5 days and received an infusion of MPTP. the experiments were divided into two parts. First, 1, 7, 14, and 21 days after surgery, the animals were submitted to the open field test. On days 21 and 22, the rats were subjected to the forced swim test and two-way active avoidance task. in the second part of the study, 24 h after neurotoxin administration, immunohistochemistry was performed to assess tyrosine hydroxylase activity. the levels of dopamine and its metabolites in the striatum were determined using high-performance liquid chromatography, and fluorescence detection was used to assess caspase-3 activation in the substantia nigra pars compacta (SNpc). Both fenofibrate as pioglitazone protected against hypolocomotion, depressive-like behavior, impairment of learning and memory, and dopaminergic neurodegeneration caused by MPTP, with dopaminergic neuron loss of approximately 33%. Fenofibrate and pioglitazone also protected against the increased activation of caspase-3, an effector enzyme of the apoptosis cascade that is considered one of the pathological features of PD. Thus, PPAR agonists may contribute to therapeutic strategies in PD. (C) 2014 Elsevier B.V. All rights reserved.
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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.