Selective changes in nicotinic acetylcholine receptor subtypes related to tobacco smoking: An immunohistochemical study

Abstract

Increases in neuronal nicotinic receptors (nAChRs) in response to nicotine exposure have been reported in cell cultures, rodent brains, and in the brains of human smokers. The present study examines alterations in α4 and α7 nAChR subunit cellular expression in human hippocampus and entorhinal cortex from normal elderly individuals with known smoking history. There were significant increases in the intensity of α4 immunoreactive neuropil, but not the number of cell bodies, in many regions of hippocampus and entorhinal cortex in smokers compared to age-matched non-smokers and ex-smokers. There was also an increase in α7 immunoreactive perikarya in the granular cell layer of dentate gyrus in smokers but not other regions examined. There was, in contrast, a significant reduction in α7 immunoreactive astrocytes in smokers and ex-smokers compared to non-smokers. These findings suggest exposure to tobacco smoke acutely upregulates α4 receptors in axon terminals and dendrites but not perikarya, whereas tobacco smoking induced down-regulation of α7 expression on astrocytes is a long-term effect. As the α4 subunit decreases with ageing and degenerative diseases such as Alzheimer's disease, whereas α7 increases in astrocytes in Alzheimer's disease, the findings further indicate the therapeutic relevance of nicotinic agonists such as nicotine.