Brain Damage-linked ATP Promotes P2X7 Receptors Mediated Pineal N-acetylserotonin Release. (1st September 2022)

• Record Type: Journal Article
• Authors: Sousa, Kassiano S.; Quiles, Caroline L.; Muxel, Sandra M.; Trevisan, Isabela L.; Ferreira, Zulma S.; Markus, Regina P.
• Is Part Of: Neuroscience. Volume 499(2022)
• Page Start: 12
• Page End: 22
• Publication Date: 2022-09-01
• Subjects: N-acetylserotonin -- MEL -- Purinergic signaling -- BzATP -- serotonin-N-acetyltransferase (SNAT) -- acetylserotonin N-methyltransferase (ASMT); ASMT acetylserotonin N-methyltransferase -- CSF cerebrospinal fluid -- EDTA ethylenediaminetetraacetic acid -- HSP heat shock protein -- HMGB high-mobility group box -- ISO Isoprenaline -- MEL melatonin -- NAd noradrenaline -- NAS N-acetylserotonin -- NF-kB nuclear factor-kappa B -- P2Y1R P2Y1 receptor -- P2X7R P2X7 receptor -- SAA serum amyloid A -- SNAT serotonin-N-acetyltransferase; Neurochemistry -- Periodicals; Neurophysiology -- Periodicals; Neurology -- Periodicals; Neurochimie -- Périodiques; Neurophysiologie -- Périodiques; Neurochemistry; Neurophysiology; Electronic journals; Periodicals; Electronic journals; 612.8
• DOI: 10.1016/j.neuroscience.2022.06.039
• Languages: English
• ISSNs: 0306-4522

Abstract

Graphical abstract: Pineal gland and ATP protects injured brain – a first stage protector of brain structures distant from injured areas. Highlights: Focal brain cell death was mimicked by injecting ATP in the right lateral ventricle. Pineal ATP low-affinity P2X7 receptor activation blocks NAS into MEL conversion. High ATP dose turns NAS into a second darkness hormone. CSF NAS is converted into MEL in the cortex, but not in the cerebellum. ATP modulation is part of a neuroprotective mechanism in areas far from the injury. Abstract: The pineal gland is a key player in surveillance and defense responses. In healthy conditions, nocturnal circulating melatonin (MEL) impairs the rolling and adhesion of leukocytes to the endothelial layer. Fungi, bacteria, and pro-inflammatory cytokines block nocturnal pineal MEL synthesis, facilitating leukocyte migration to injured areas. ATP is a cotransmitter of the noradrenergic signal and potentiates noradrenaline (NAd)-induced MEL synthesis via P2Y1 receptor (P2Y1 R) activation. Otherwise, ATP low-affinity P2X7 receptor (P2X7R) activation impairs N-acetylserotonin (NAS) into MEL conversion in NAd incubated pineals. Here we mimicked a focal increase of ATP by injecting low (0.3 and 1.0 µg) and high (3.0 µg) ATP in the right lateral ventricle of adult rats. Nocturnal pineal activity mimicked the in culture data. Low ATP doses increased MEL output, while high ATP dose and the P2X7R agonist BzATP (15.0–50.0 ng) increased NAS pineal and blood content. In the brain, the response was structure-dependent. There was an increase in cortical and no change in cerebellar MEL. These effects were mediated by changes in the expression of coding genes to synthetic and metabolizing melatonergic enzymes. Thus, the pineal gland plays a role as a first-line structure to respond to the death of cells inside the brain by turning NAS into the darkness hormone.