Prenatal methanol exposure alters expression of dopaminergic markers in the striatum of a parkinsonian mouse model

Abstract

Parkinson's disease (PD) is a neurodegenerative disorder characterized by a loss of substantia nigra (SN) dopaminergic neurons. The etiology of PD remains unknown. This study proposes that prenatal exposure to methanol (MeOH) will sensitize the developing dopamine system to post‐natal challenges. Pregnant mice were treated with MeOH (4 mg/kg) during gestational days 8‐12. At 12 weeks of age, the control and MeOH exposed offspring were treated with 1‐methyl‐4‐phenyl‐1,2,3,6,‐tetrahydropyridine (MPTP) for 7 days. Markers of the dopaminergic system such as tyrosine hydroxylase (TH), aromatic amino acid decarboxylase (AADC) as well as dopamine (DA) and its metabolites were determined in the striatum of control and MeOH offspring. The results show that striatal TH and dopamine were decreased by 25% and 44.2% respectively, in MeOH offspring. DA, TH and LAAD expression were decreased in a dose dependent manner by MPTP in both the control and MeOH offspring. The MeOH groups with an already 25% reduction, showed a reduced rate of decline of TH or resistance to MPTP. In summary, evidence from preliminary histological study indicates that MeOH causes a failure of TH cell migration into SN compacta. This may reduce the TH projection fibers to the striatum and code for a more resilient population of TH cells. The outcome is a positive test of concept that a sensitization stage underlies PD.