Molecular Mechanisms of Aberrant Neuroplasticity in Autism Spectrum Disorders (Review)

Abstract

This review presents the analysis and systematization of modern data on the molecular mechanisms of autism spectrum disorders (ASD) development. Polyetiology and the multifactorial nature of ASD have been proved. The attempt has been made to jointly review and systematize current hypotheses of ASD pathogenesis at the molecular level from the standpoint of aberrant brain plasticity. The mechanism of glutamate excitotoxicity formation, the effect of imbalance of neuroactive amino acids and their derivatives, neurotransmitters, and hormones on the ASD formation have been considered in detail. The strengths and weaknesses of the proposed hypotheses have been analyzed from the standpoint of evidence-based medicine. The conclusion has been drawn on the leading role of glutamate excitotoxicity as a biochemical mechanism of aberrant neuroplasticity accompanied by oxidative stress and mitochondrial dysfunction. The mechanism of aberrant neuroplasticity has also been traced at the critical moments of the nervous system development taking into account the influence of various factors of the internal and external environment. New approaches to searching for ASD molecular markers have been considered.

Transtorno do Espectro Autista em Crianças: Uma Revisão Sistemática sobre o Aumento da Incidência e Diagnóstico

“…As características dos estudos incluídos nesta revisão sistemática foram sintetizadas na Quadro 2. Quinze artigos foram elegíveis para inclusão no presente estudo, consistindo em três estudos de incidência (Accordino et al, 2017;Demer, 2018;Hand et al, 2021), um estudo prognóstico (Andoy Galvan et al, 2020), dois guias de prática clínica (Churruca et al, 2019;SBP, 2019), dois estudos transversais (Davidovitch et al, 2021;Penner et al, 2018), quatro estudos de prevalência (Guthrie et al, 2019;Hyman et al, 2020); Maenner et al 2021;Málaga et al, 2019), uma revisão integrativa (Lavor et al, 2021), uma revisão sistemática (Anashkina & Erlykina, 2021) e um estudo de rastreamento (Monteiro et al, 2019).…”

“…Os artigos são procedentes dos Estados Unidos (n=6) (Accordino et al, 2017;Guthrie et al, 2019;Hand et al, 2021;Hyman et al, 2020;Demer, 2018;Monteiro et al, 2019), Rússia (n=1) (Anashkina & Erlykina, 2021), Malásia (n=1) (Andoy Galvan et al, 2020), Austrália (n=1) (Churruca et al, 2019), Israel (n=1) (Davidovitch et al, 2021), Argentina (n=1) (Málaga et al, 2019), Brasil (n=2) (Lavor et al, 2021) e Canadá (n=1) (Penner et al, 2018).…”

“…Frisa-se que todos os estudos concordam em um diagnóstico antecipado, com foco na melhora da qualidade de vida do paciente, e um dos mais promissores, talvez, seja através da reabilitação genética (Anashkina & Erlykina, 2021)durante os períodos perinatal e pós-natalprocesso esse que carece de investimentos nacionais.…”

The role of HIF-1α silencing in late pregnancy hypoxia-induced autism-like behavior in rat offspring

“…The complex etiology, pathogenesis, and diagnosis of ASD are subjects of intense discussion [18][19][20] . The most effective treatment for ASD is early behavior correction 2122 , although the curative effect is limited.…”