The Age-Related Effect of Nicotine on the Expression of Neuroprotective Genes in Ventral Tegmental Area and Substantia Nigra

Abstract

Selective degeneration of dopaminergic neurons, which are predominantly located in the substantia nigra (SN) of the midbrain, is one of the hallmarks of Parkinson’s disease (PD). Large-scale microarray experimental data revealed several genes with significantly differential expression between the ventral tegmental area (VTA) and the SN dopamine (DA) neurons. Several epidemiological studies have additionally indicated nicotine-mediated neuroprotection in PD patients. Based on the strong evidence implicating lipoprotein lipase (LPL), pituitary adenylate cyclase-activating polypeptide and gastrin-releasing peptide genes in neuroprotection, this letter investigates area- and age-specific nicotine regulation of these genes’ expression in the VTA and SN of different age groups (3 months, 12 months, and 24 months) in an in vivo animal model. Our in vivo rat model results suggest that out of these genes, only the LPL gene has significantly differential expression between the VTA and SN in the senior age group (24 months). Nicotine treatment did not upregulate the neuroprotective genes in adult and senior groups (12 and 24 months). Differential expression of the LPL gene in the senior population may contribute to the different survival rates of DA neurons within the VTA and SN. However, downregulation by nicotine suggests that these genes may not be related to the nicotine-mediated neuroprotection known to reduce the risks of PD. Our results suggest that nicotine may not play an important role in the regulation of neuroprotective gene expressions, while providing new insights into the role of nicotine in PD.