Research: “Abnormal glutamate release in aged BTBR mouse model of autism”

It is currently unknown whether the neurobiological findings present in young adults with autism spectrum disorder (ASD) are also present in older adults. Autism spectrum disorder (ASD) is a neurodevelopmental disorder involving deficits in information processing. Inhibitory and excitatory synapses are essential in information processing in the brain. Furthermore, previous studies have found that ASD likely arises from an imbalance between inhibitory and excitatory synaptic transmission. However, due to a lack of studies of ASD in old age, synaptic structures in adults are poorly understood. In a study by researchers at  Shanxi Provincial People’s Hospital, researchers compared the morphology and synaptic function of excitatory synapses in aged mice with low level sociability (BTBR) to mice with high level sociability (control mice). Researchers labeled pre-synaptic protein and post-synaptic protein Shank3. Shank3 is found in excitatory synapses and is highly associated with ASD. Through image analysis, researchers then quantified and noted the colocalization of pre- and post- synapses in BTBR aged mice and control mice. Results indicated there were no significant differences in the number of excitatory synapses, expression of Shank3 protein or shape of dendritic spines in aged BTBR mice and control mice. However, the baseline and evoked glutamate release in aged BTBR mice was lower than control mice. Glutamate is the principal excitatory neurotransmitter in the brain and is important in regulating the balance between neuronal excitation and inhibition. The findings in this study suggest that, unlike in children, ASD in adults is hypoglutamatergic. Thus, there is an age-related glutamate change that occurs in individuals with ASD: excessive glutamate or over activation in the autistic brain at a young age and deficient glutamate or over inhibition in the autistic brain at old age.