Nicotinic acetylcholine receptors during prenatal development and brain pathology in human aging

Nicotinic acetylcholine receptor (nAChRs) proteins and gene transcripts are already present in human prenatal brain and spinal cord at 4-6 weeks gestation, and a clear age-related increase in number of nAChRs was apparent during first trimester. In pens, there was also a parallel increase in the alpha 7 mRNA level with age. The highest specific binding of [H-3]epibatidine and [H-3]cytisine was detected in spinal cord, pens and medulla oblongata, and binding of [I-125]alpha-bungarotoxin was highest in spinal cord, medulla oblongata and mesencephalon. From the late fetal stage brain nAChRs have been shown to fall with increasing age. During aging (between 40 and 100 years) high affinity nicotine binding in the frontal cortex decreases in parallel with glutamate NMDA receptor binding ([H-3]MK801). In the hippocampal formation and entorhinal cortex nicotine binding also declines with age, in common with [I-125]alpha-bungarotoxin in the entorhinal cortex, but NMDA receptor binding remains unchanged. These reductions in nicotine binding with age may predispose the neo- and archicortex to the loss of nAChRs observed in age-associated neurodegenerative conditions. By contrast no loss in nAChR binding with aging is observed in the thalamus and only after the 70th decade in the striatum, although in Alzheimer's disease, Parkinson's disease and Lewy body dementia deficits in nAChRs are observed in these areas and may be associated with specific disease-related processes. (C) 2000 Elsevier Science B.V. All rights reserved.