Nicotine-Induced Neuroprotection in Rotenone In Vivo and In Vitro Models of Parkinson’s Disease: Evidences for the Involvement of the Labile Iron Pool Level as the Underlying Mechanism
Neurotoxicity Research
Authors and affiliations
Camila Mouhape, Gustavo Costa, Margot Ferreira, Juan Andrés Abin-Carriquiry, Federico Dajas, Giselle Prunell
ORIGINAL ARTICLE
First Online: 13 July 2018
Abstract
Parkinson’s disease (PD) is characterized by the degeneration of the dopaminergic neurons in the substantia nigra pars compacta (SNpc). Clinical and experimental evidence suggest that the activation of the nicotinic acetylcholine receptor (nAChR) could
be protective for PD. In this study, we investigated the neuroprotective capacity of nicotine in a rat PD model. Considering that iron metabolism has been implicated in PD pathophysiology and nicotine has been described to chelate this metal, we also
studied the effect of nicotine on the cellular labile iron pool (LIP) levels. Rotenone (1 μg) was unilaterally injected into the median forebrain bundle to induce the degeneration of the nigrostriatal pathway. Nicotine administration (1 mg/K, s.c. daily
injection, starting 5 days before rotenone and continuing for 30 days) attenuated the dopaminergic cell loss in the SNpc and the degeneration of the dopaminergic terminals provoked by rotenone, as assessed by immunohistochemistry. Furthermore, nicotine
partially prevented the reduction on dopamine levels in the striatum and improved the motor deficits, as determined by HPLC-ED and the forelimb use asymmetry test, respectively. Studies in primary mesencephalic cultures showed that pretreatment with
nicotine (50 μM) improved the survival of tyrosine hydroxylase-positive neurons after rotenone (20 nM) exposure. Besides, nicotine induced a reduction in the LIP levels assessed by the calcein dequenching method only at the neuroprotective dose. These
effects were prevented by addition of the nAChRs antagonist mecamylamine (100 μM). Overall, we demonstrate a neuroprotective effect of nicotine in a model of PD in rats and that a reduction in iron availability could be an underlying mechanism.

Keywords
Parkinson’s disease Rotenone Nicotine Labile iron pool Neuroprotection

https://link.springer.com/article/10.1007%2Fs12640-018-9931-1

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