The role of purinergic signaling in depressive disorders.

摘要: The purinergic signaling system consists of transporters, enzymes and receptors responsible for the synthesis, release, action extracellular inactivation adenosine 5'-triphosphate (ATP) its breakdown product adenosine. actions ATP are mediated ionotropic P2X metabotropic P2Y receptor subfamilies, whilst by P1 receptors. Purinergic pathways widely expressed in central nervous (CNS) participate normal pathological functions. Among receptors, P2X7 (P2rx7) has received considerable interest both basic clinical neuropsychiatric research because profound effects animal CNS pathology potential involvement as a susceptibility gene mood disorders. Although genetic findings were not always consistently replicated, several studies demonstrated that single nucleotide polymorphisms (SNPs) human (P2RX7) show significant association with major depressive disorder bipolar disorder. Animal revealed knock-down or pharmacological antagonism leads to reduced depressive-like behavior, attenuated response mania-model alterations stress reactivity. A mechanism P2rx7 activation on related behavior is increased glutamate extrasynaptic NMDA subsequent enduring changes neuroplasticity. In addition, dysregulation monoaminergic transmission HPA axis reactivity could also contribute observed behavior. Besides P2rx7, inhibition A1 A2A mediate antidepressant-like experiments. conclusion, despite contradictions between existing data, these point therapeutic