Title:Possibility that the Onset of Autism Spectrum Disorder is Induced by Failure of the Glutamine-Glutamate Cycle
Volume: 14
Author(s): Koichi Kawada*, Nobuyuki Kuramoto and Seisuke Mimori
Affiliation:
- The Institute of Prophylactic Pharmacology, Kita-Shinagawa, Shinagawa, 140-0001, Tokyo,Japan
Keywords:
Autism spectrum disorder, glutamine-glutamate cycle, endoplasmic reticulum stress.
Abstract:
Autism spectrum disorder (ASD) is a neurodevelopmental disease, and the number of patients
has increased rapidly in recent years. The causes of ASD involve both genetic and environmental
factors, but the details of causation have not yet been fully elucidated. Many reports have investigated
genetic factors related to synapse formation, and alcohol and tobacco have been reported
as environmental factors. This review focuses on endoplasmic reticulum stress and amino acid cycle
abnormalities (particularly glutamine and glutamate) induced by many environmental factors.
In the ASD model, since endoplasmic reticulum stress is high in the brain from before birth, it is
clear that endoplasmic reticulum stress is involved in the development of ASD. On the other hand,
one report states that excessive excitation of neurons is caused by the onset of ASD. The glutamine-
glutamate cycle is performed between neurons and glial cells and controls the concentration
of glutamate and GABA in the brain. These neurotransmitters are also known to control synapse
formation and are important in constructing neural circuits. Theanine is a derivative of glutamine
and a natural component of green tea. Theanine inhibits glutamine uptake in the glutamine-glutamate
cycle via slc38a1 without affecting glutamate; therefore, we believe that theanine may prevent
the onset of ASD by changing the balance of glutamine and glutamate in the brain.
