Abstract

POMILIO, Alicia Beatriz et al. Bases neuroquímicas de la transmetilación aberrante de neuroaminas y su relación con el metabolismo de la vitamina B₁₂ y el ácido fólico. Acta bioquím. clín. latinoam. [online]. 2022, vol.56, n.4, pp.433-468. ISSN 0325-2957.

Alterations that may occur in the methylation process via folate and methionine cycles, resulting in dysfunctions evidenced in psychiatric disorders such as schizophrenia are analysed. The changes in neurobiological systems related to the pathogenesis of schizophrenia, in particular pathological transmethylation, are discussed highlighting research that contributed to prove it, including those of this research group. Mitochondrial dysfunction, oxidative stress, proteomics, and epigenetic regulations such as DNA methylation are discussed. Dysfunctions of serotonin signaling and HTR2A gene are involved in the development of schizophrenia. The neurometabolic alteration of schizophrenia was investigated, focusing on indolealkylamines. An exhaustive correlation between transmethylation activity, monoamine oxidase (MAO) hypoactivity, intra- and extracellular MAOs alteration, and the occurrence of methylated indolealkylamines in urine of several schizophrenic phenotypes, with 94.1% transmethylation activity above normal were observed. It was demonstrated in vivo in rabbits that N,N-dimethyltryptamine remained in the brain, even 7 days after administration, unlike serotonin and tryptamine. Mainly sigma-1 and 5-HT2A-mGlu2 receptors as well as SERT and VMAT2 transporters made it possible to explain this behaviour.

Keywords : Carbon-1 metabolism; Aberrant methylation; Mitochondrial dysfunction; Oxidative stress; Serotonergic pathway; N,N-dimethyltryptamine.

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