The P2X7 receptor antagonist Brilliant Blue G attenuates contralateral rotations in a rat model of Parkinsonism through a combined control of synaptotoxicity, neurotoxicity and gliosis

Inhibiting purinergic P2X7 receptors with the antagonist brilliant blue G is neuroprotective in an intranigral lipopolysaccharide animal model of Parkinson's disease

“…This finding supports an earlier study, which reported that P2X7R antagonists significantly prevent 6-hydroxydopamine-induced depletion of striatal DA stores (23,24). However, other studies have reported that P2X7R deficiency or inhibition is not effective against 1-methyl-4-phenylpyridinium or rotenone-induced DA loss in chemical PD models (25).…”

“…Therefore, the expression of P2X7R in microglia appeared to be a critical factor in mediating microglial activity and stimulating the loss of DA neurons in PD. These observations are consistent with the suggestion that P2X7R is critical in neuroinflammation, which is observed during the pathogenesis of a variety of neurodegenerative diseases (14,17,18,20–23). …”

“…Several lines of evidence have confirmed that the P2X7R pathway causes neuronal injury, leading to the progression of neurodegeneration (17,20). Although reports on the role of P2X7R in PD are rare and contradictory, previous studies have established that this receptor is upregulated in an animal model of PD (23,24), although a P2X7R antagonist was not associated with the reduction of DA cell loss (24,25). However, a previous study provided evidence supporting the suggestion that P2X7R antagonism attenuates the neuronal dysfunction and damage in an animal model of PD (23).…”

Activation of P2X7 receptors in the midbrain periaqueductal gray of rats facilitates morphine tolerance

“…In the nervous system, they are involved in the modulation of neurotransmitter release, as well as microglial and astroglial activation (Sperlagh et al, 2006). The activation of P2X 7 receptor on neuronal or non-neuronal cells is related to many brain disorders such as trauma (Kimbler et al, 2012;O'Hare Doig and Fitzgerald, 2015), Alzheimer's disease (Diaz-Hernandez et al, 2012;Sanz et al, 2014), Parkinson's disease (Carmo et al, 2014;Liu et al, 2013), and multiple sclerosis (Grygorowicz et al, 2011).…”

Purinergic signaling in Parkinson's disease. Relevance for treatment

“…Expression of these heteromers in striatal cells indicates that D 1 and D 2 receptor segregation in different neuronal types is not complete. Polymorphisms in the P2X 7 gene are associated in a Chinese population with sporadic forms of PD [124] and antagonists of the P2X 7 receptor are beneficial in animals models of PD [125,126]. These data link ionotropic purinergic transmission with striatal function and PD.…”