P2X7 Receptor Signaling in Stress and Depression

Author(s)

Ribeiro, Deidiane Elisa ; Roncalho, Aline Lulho ; Glaser, Talita ; Ulrich, Henning ; Wegener, Gregers ; Joca, Samia

• Document type: Journal article
• Source: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES; v. 20, n. 11, p. 26-pg., 2019-06-01.

Abstract

Stress exposure is considered to be the main environmental cause associated with the development of depression. Due to the limitations of currently available antidepressants, a search for new pharmacological targets for treatment of depression is required. Recent studies suggest that adenosine triphosphate (ATP)-mediated signaling through the P2X7 receptor (P2X7R) might play a prominent role in regulating depression-related pathology, such as synaptic plasticity, neuronal degeneration, as well as changes in cognitive and behavioral functions. P2X7R is an ATP-gated cation channel localized in different cell types in the central nervous system (CNS), playing a crucial role in neuron-glia signaling. P2X7R may modulate the release of several neurotransmitters, including monoamines, nitric oxide (NO) and glutamate. Moreover, P2X7R stimulation in microglia modulates the innate immune response by activating the NLR family pyrin domain containing 3 (NLRP3) inflammasome, consistent with the neuroimmune hypothesis of MDD. Importantly, blockade of P2X7R leads to antidepressant-like effects in different animal models, which corroborates the findings that the gene encoding for the P2X7R is located in a susceptibility locus of relevance to depression in humans. This review will discuss recent findings linked to the P2X7R involvement in stress and MDD neuropathophysiology, with special emphasis on neurochemical, neuroimmune, and neuroplastic mechanisms. (AU)

• FAPESP's process: 18/08426-0 - Indole alkaloid sub products of Maqui (Aristotelia chilensis) processing as food additives to Alzheimer's Disease treatment
• Grantee: Alexander Henning Ulrich
• Support Opportunities: Regular Research Grants
• FAPESP's process: 15/13345-1 - Huntington's disease: Huntingtin roles during cell fate decision
• Grantee: Talita Glaser
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 12/50880-4 - Stem cells: from basic studies of kinin and purinergic receptor roles towards therapeutical applications
• Grantee: Alexander Henning Ulrich
• Support Opportunities: Research Projects - Thematic Grants