Pathophysiological mechanisms of autism in children

Abstract

Based on the analysis of literature, the authors describe the neuropathophysiological mechanism of the formation of synapses, synaptic transmission and plasticity, which may underlie the pathogenesis of autism. The results of some studies confirm the involvement of aberrant expression of genes and proteins of synaptic contacts, cell adhesion molecules p120ctn, CNTN5, CNTN6, activation of NMDA glutamate, TrkB, p75 receptors, Ca2+-input, BDNF, serotonin and testosterone. This leads to an imbalance in the exciting, inhibitory synaptic transmission and forms of synaptic plasticity, including long-term potentiation (LTP) and long-term depression (LTD) at the level of individual neurons and their chains due to suppression of GABA synthesis, expression of its ionotropic and metabotropic receptors, G proteins, NGF, TrkA receptors, a reduction in the number of GABAergic neurons, their contacts and disruption of differentiation. The pathology of the nuclei of the thalamus, especially the reticular nucleus (RN), is associated with a disturbance of the expression of the subunits of metabotropic GABAβ receptors, Ca2+ channels, GABA excretion and the work of chlorine transmitters. These failures do not ensure the inhibitory effect of OC on the exciting associative and ventral nuclei of the thalamus, nor modify the incoming information to the cerebral cortex (CC) from these thalamus nuclei, the dentate gyrus of the hippocampus and the nuclei of the reticular formation. Information propagating into the somatosensory and associative regions of CC is not modified by mirror neurons (MN) when performing arbitrary actions, which prevents the formation of an adequate image in the neural networks of the associative cortex and promotes the development of hyperexcitability, irritability, increased visual and auditory sensitivity, anxiety, and the ability to form a holistic image based on the actions of other people.