Hungarian Brain Research Program(NAP2022-I-1/2022)
National Laboratory of Translational Neuroscience (TINL)(RRF-2.3.1-21-2022-00011)
(EKÖP-2024-68)
Early-life stress may increase the risk of neuropsychiatric disorders via immune activation.
While the purinergic signaling pathway is implicated in psychiatric disorders, the
specific role of the P2X7 receptor (P2X7R) in anxiety, depression, and childhood trauma
still requires further clarification. Upon chronic stress, excessive ATP release activates
purinergic P2X7R signalling in the brain contributing to long-lasting neuroinflammation,
which potentially promotes the development of psychiatric disorders. There is also
a putative link between the P2X7 receptor gene, located on chromosome 12q24, and the
development of anxiety and depression. This review aims to systematically examine
how P2X7R contributes to the pathophysiology of anxiety and depressive disorders,
with a particular focus on early-life stress (ELS). It offers a comprehensive synthesis
of the current findings, emphasizing the previously unexplored intersections between
P2X7R signaling, early-life stress, and psychiatric disorders. These interactions
may shape long-term neuroinflammation, contributing to the development of anxiety
and depression, and offer new insights into potential therapeutic targets. The review
integrates the role of P2X7R regarding both indirect mechanisms—such as the modulation
and long-term transmission of neuroinflammation following environmental stressors
and vulnerability—and direct genetic associations with psychiatric conditions, including
the influence of single-nucleotide polymorphisms (SNPs), haplotypes, and other variants
within the P2X7 gene. Special emphasis is placed on the impact of early-life stress,
drawing primarily on preclinical findings to elucidate underlying mechanisms.
