PET Study of the Nicotinic Receptors in Human : Brain Distribution and Quantification

PET is a non -invasive technique that allow to study, in vivo in human, the neurotransmission system. Thanks to the development of radiotracers that are selective for the binding site of the neurotransmitter, several system have been studied such as the dopaminergic, GABAergic system.

However, the in vivo study of the cholinergic system, was hampered the lack of suitable radiotracer. The cholinergic system is an important neurotransmitter system in human brain which exact rule remains unclear. It is involved in cognition, and memory and it is altered early in several neurodegeneratives diseases such as Parkinson and Alzheimer diseases.

The nicotinic receptors are one target of the cholinergic neurotransmission (together with muscarinic receptors), that are of importance since postmortem studies have showed their early alteration in neurodegeneratives diseases. Moreover, as they are located mostly on presynaptic part of the cholinergic terminations, their labelling can be of great interest for the study of the integrity of the cholinergic fibres.

Post-mortem studies have shown a reduction of the nicotinic receptors density in Alzheimer's disease in temporal cortex and hippocampus. Similarly, in Parkinson's diseases, nicotinic receptor density have been shown to be reduced in fronto-temporal cortex and in pedoculo-pontin nuclei. Recently, point mutation on nicotinic receptor sub-units (alpha4 or beta2) have been objectived in a familial epilepsy: the Autosomic Dominant Noctural Frontal Lobe Epilepsy (ADNFLE). Nicotinic receptor are also involved in tobacco addiction, as they are the main brain target of the nicotine from the cigarette smoking. Human post-mortem studies and animal models suggest that nicotinic receptor density is increased in chronic smoker.

The in vivo study of these receptors will bring new insight in the understanding of the physiopathology of nicotinic receptor in several neurodegeneratives diseases.