Abstract
It has been observed that there is a lower Parkinson’s disease (PD) incidence in tobacco users. Nicotine is a cholinergic agonist and is the principal psychoactive compound in tobacco linked to cigarette addiction. Different studies have shown that nicotine has beneficial effects on sporadic and genetic models of PD. In this work we evaluate nicotine’s protective effect in a Drosophila melanogaster model for PD where Synphilin-1 (Sph-1) is expressed in dopaminergic neurons. Nicotine has a moderate effect on dopaminergic neuron survival that becomes more evident as flies age. Nicotine is beneficial on fly survival and motility increasing tyrosine hydroxylase and dopamine levels, suggesting that cholinergic agonists may promote survival and metabolic function of the dopaminergic neurons that express Sph-1. The Sph-1 expressing fly is a good model for the study of early-onset phenotypes such as olfaction loss one of the main non-motor symptom related to PD. Our data suggest that nicotine is an interesting therapeutic molecule whose properties should be explored in future research on the phenotypic modulators of the disease and for the development of new treatments.
Highlights
It has been observed that there is a lower Parkinson’s disease (PD) incidence in tobacco users
In zebra fish where the actual absorption is much higher because nicotine is supplemented in the water where the fish swim and it is absorbed through the skin, the range of nicotine concentrations used is from 5 to 100 μM28
Given that the concentration of nicotine chosen in our study for feeding experiments is 24 μM, it is reasonable to estimate that the actual concentration in the hemolymph or the fly brain is about 200 nM
Summary
It has been observed that there is a lower Parkinson’s disease (PD) incidence in tobacco users. Nicotine is beneficial on fly survival and motility increasing tyrosine hydroxylase and dopamine levels, suggesting that cholinergic agonists may promote survival and metabolic function of the dopaminergic neurons that express Sph-1. Sph-1 appears to be important for synaptic connections but its specific functions, just as those of α-Syn, are unknown[10] It has been proposed, that Sph-1 might be involved in supporting proteasome degradation, and given its strong interaction with α-Syn, it could play a central role in Lewy body formation and synaptic. It is of crucial importance to search for molecules that might help maintain dopaminergic neuron function or prevent degeneration caused by protein accumulation[16]. One of these potentially protective molecules is nicotine, the primary psychoactive substance of tobacco. Nicotine is known as an acetylcholine receptor agonist that promotes cellular excitability, the mechanisms underlying its cytoprotective mechanisms are unknown[20]
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