Serotonergic mechanisms associated with experimental models of hypoxia: A systematic review.

PURPOSE: The aim of this systematic review was to explore and discuss the literature concerning the effects of hypoxia or anoxia during the perinatal period on the serotoninergic network in rodents, through mechanisms that lead to changes in serotonergic neurons, levels, segments of central nervous system affected, 5-HT transporter, and 5-HT receptor. METHODS: Literature searches were performed in Embase, Medline (PubMed), Web of Science, and SCOPUS, from April to July 2021, with a total of 1045 published studies found. Using a predefined protocol, as registered on the CAMARADES website, 10 articles were included in this review. The PRISMA statement was used for reporting this systematic review. The internal validity was assessed using the SYRCLE's risk of bias tool. RESULTS: Our main findings show that hypoxia in the first days of postnatal life led to a disturbance in the serotonergic system with reduced in 5-HT fibers, reduced brain levels of 5-HT and 5-HIAA, reduced SERT protein expression, and reduced receptor 5-HT7 . Putative mechanisms involving damage in the serotoninergic system include retrograde cell death resulting from primary damage mainly in forebrain areas, which impairs remote areas including serotonergic raphe nuclei. Other probable mechanisms associated with the serotoninergic network damage may be triggered by excitotoxic lesion and neuroinflammation. CONCLUSION: Hypoxia at the beginning of an animal's life leads to modification of the serotonergic components associated with putative mechanisms that include cell damage and neuroinflammation.

L-tryptophan administration and increase in cerebral serotonin levels: Systematic review.

The amino acid tryptophan (2-Amino-3-(lH-indol-3-yl)-propanoic acid; Trp) is a precursor of the neurotransmitter serotonin (5-hydroxytryptamine; 5-HT) that performs various brain functions. The administration of Trp is used in experimental studies to manipulate the serotonergic system, however the dose of Trp required to raise brain 5-HT levels is controversial. The aim of this study was to systemically review the effect of the administration of different doses of Trp on cerebral 5-HT levels. Two independent authors conducted a systematic review in the electronic databases. Twenty-five studies were included in the present review. Trp was administered orally, intraperitoneally or subcutaneous in adult animals. The brain 5-HT levels elevated after Trp administration in different intensities, dependent of the brain region evaluated and the time of administration. Further studies are needed to assess the dose-response of Trp administration to brain 5-HT levels.