Altered Nucleotide Receptor Expression in a Murine Model of Cerebral Malaria

Abstract

In cerebral malaria, the most severe complication of malaria, both neurotransmission mechanisms and energy metabolism are affected. To understand how metabolic changes modify neurotransmission, we examined P2 receptor expression in a murine model of cerebral malaria. Quantitative polymerase chain reaction experiments revealed that parasite deposition was greatest in the cerebellum, compared with other areas of the brain, suggesting a correlation between brain parasitemia and loss of control of movement. Infected mice showed modified patterns of expression of P2 receptor subtype messenger RNA (mRNA), depending on both the specific purinergic receptor and the cerebral region analyzed. Immunohistochemical studies indicated altered levels of protein expression by these receptors in infected brains and, in some cases, a pattern of expression different from that noted in control mice. These differences in both the amount of mRNA and the protein distribution of P2 receptors observed in the different brain sites in infected mice suggest an important role for P2 receptors in either provoking cerebral damage or conferring neuroprotection.

Sustained Release of Prostaglandin E2in Fibroblasts Expressing Ectopically Cyclooxygenase 2 Impairs P2Y-Dependent Ca2+-Mobilization

“…Real-time PCR was conducted with SYBR Green (Roche) on a MyiQ Real-Time PCR System (Bio-Rad). The TaqMan probes for mouse EP1, EP2, EP3, EP4, P2Y2, and P2Y4 used in this study were purchased from Applied Biosystems and experiments for validation of amplification efficiency were performed for each TaqMan probe set [28, 29]. PCR thermocycling parameters were 95°C for 10 min, 40 cycles of 95°C for 15 s, and 60°C for 1 min.…”

Gene profiling analysis reveals the contribution of CD24 and P2Y6R to the susceptibility of young rats to Plasmodium berghei infection

“…This decrease could lead to an alteration of P2Y6R functions and, consequently, of the related down stream pathways. In a very recent study concerning the expression of nucleotide receptors in a mouse model of cerebral malaria, it was observed that the expression of most P2 receptors was decreased in the thalamus‐hypothalamus of the brains of infected mice, suggesting a role for these receptors in the pathophysiology of cerebral malaria (Marin‐Garcia et al ., 2009). The expression level of P2Y6R was not evaluated in this murine malaria model.…”

Purinergic modulation of the immune response to infections

“…Indeed, mammalian RBCs express ADORA2b and several P2Y and P2X receptors on their surface [ 85 ]. In experimental cerebral malaria the expression of several P2X and P2Y receptors is altered after P. berghei infection [ 86 ]. However, to date little is known about purinergic modulation of malaria-specific immune response.…”