Nicotinic receptors in human brain: topography and pathology

Abstract

Brain nicotinic acetylcholine receptors (nAChR) are a class of ligand-gated channels composed of alpha and beta subunits with specific structural, functional and pharmacological properties. They participate in the physiological and behavioural effects of acetylcholine and mediate responses to nicotine. They are associated with numerous transmitter systems and their expression is altered during development and ageing as well as in diseases such as autism, schizophrenia, Alzheimer's disease, Parkinson's disease and Lewy body dementia. Nicotinic receptors containing a number of different subunits are highly expressed during early human development. Disorders believed to be associated with abnormal brain maturation involve deficits in both alpha4beta2, in the case of autism, and alpha7 possibly in addition to alpha4beta2 nAChRs in the case of schizophrenia. In ageing and age-related neurodegenerative disorders nAChR deficits are predominantly associated with alpha4-containing receptors, although some studies also indicate the involvement of alpha3 and alpha7 subunits. Whilst ageing appears to be associated with reductions in subunit mRNA as well as protein expression, in Alzheimer's disease only protein loss is apparent. Nicotinic therapy may be of benefit in a number of neurological conditions, however studies evaluating further both the distribution of specific subunit involvement and the correlation of nAChR deficits with clinical symptoms are required to inform therapeutic strategy.