Molecular and cellular mechanisms of synaptopathies in autism

Abstract

Autism is a complex neurodevelopmental condition that includes impairments in social interaction poor language and communication skills together with repetitive behaviors. Synapses are essential components of neurons that needed for the travel of information throughout the nervous system to adjust different behaviors. Thus, optimal synaptic communication is required for proper brain physiology, and slight deviation of synapse function early in life can lead to neurodevelopmental disorders among which is autism. Synaptopathy arises from alterations that affecting the integrity and/or functionality of synapses, can contribute to synaptic pathologies as etiological mechanism of autism. Based upon the blood biomarkers of autism, increased platelet serotonin (5- HT), suggest that increased 5-HT uptake or storage in the presynaptic neuron would lead to decreased brain 5-HT. A relationship between autistic behavior and dysfunctions in the midbrain dopaminergic system was also hypothesized. While dysfunction of the nigrostriatal circuit leads to stereotyped behaviors, a dysfunction in mesocorticolimbic circuit leads to social deficits. Additionally, imbalanced GABAergic/ glutamatergic neurotransmissions in plasma of autistic children demonstrates glutamate excitotoxicity as etiological mechanism of this disorder. Our most recent study proved that GABA synaptopathy promotes caspase 3 and caspase 9 as pro-apoptotic markers. In this talk, relationship between synaptopathies, apoptosis, mitochondrial dysfunction, and impaired gut microbiota as etiological mechanisms of autism will be discussed. Understanding common causes and mechanisms of autismâ associated synaptic dysfunction could offer novel clues toward synapseâ based treatment strategy and early intervention of autism.

Author(s): Afaf El Ansary

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