Autism is a developmental disorder of unknown aetiopathology and lacking any specific pharmacological therapeutic intervention.
Neurotransmitters such as
serotonin,
gamma-aminobutyric acid (
GABA) and
acetylcholine have been implicated. Abnormalities in
nicotinic acetylcholine receptors have been identified including cortical loss of binding to the alpha4/beta2 subtype and increase in cerebellar alpha7 binding. Receptor expression (
mRNA) has not so far been systematically examined. This study aims to further explore the role of
nicotinic receptors in
autism by analysing
nicotinic receptor subunit
mRNA in conjunction with
protein levels and receptor binding in different brain areas. Quantitative RT-PCR for alpha4, alpha7 and beta2 subunit
mRNA expression levels; alpha3, alpha4, alpha7 and beta2
subunit protein expression immunochemistry and specific radioligand receptor binding were performed in adult
autism and control brain samples from cerebral cortex and cerebellum. Alpha4 and beta2
protein expression and receptor binding density as well as alpha4
mRNA levels were lower in parietal cortex in
autism, while alpha7 did not change for any of these parameters. In cerebellum, alpha4
mRNA expression was increased, whereas
subunit protein and receptor levels were decreased. Alpha7 receptor binding in cerebellum was increased alongside non-significant elevations in
mRNA and
protein expression levels. No significant changes were found for beta2 in cerebellum. The data obtained, using complementary measures of receptor expression, indicate that reduced gene expression of the
alpha4beta2 nicotinic receptor in the cerebral cortex is a major feature of the neurochemical pathology of
autism, whilst post-transcriptional abnormalities of both this and the alpha7 subtype are apparent in the cerebellum. The findings point to dendritic and/or synaptic
nicotinic receptor abnormalities that may relate to disruptions in cerebral circuitry development.