Effects of Environmental Enrichment on Neurotrophins in an MPTP-Induced Parkinson's Disease Animal Model: A Randomized Trial

The aim of this study was to investigate the effect of environmental enrichment (EE) on neurotrophin expression in an animal model of Parkinson's disease (PD). PD was induced via intraperitoneal injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Male mice (N = 42) were randomly divided into 3 groups: control, MPTP + standard condition (SC), and MPTP + EE. The groups were raised separately for 28 days. On Day 21 they received 1 injection (20 mg/kg MPTP or saline for MPTP and control groups, respectively) every 2 hr for a total of 4 injections. Animals were sacrificed 7 days after the final injection and their brains were immediately removed. Neurotrophins and messenger ribonucleic acid (mRNA) expression levels were measured. The BCL-2/Bax ratio significantly increased in the MPTP + EE compared to the MPTP + SC group. Nerve growth factor (NGF) mRNA level was upregulated (but not significantly) in the MPTP + EE compared to the MPTP + SC group. Tyrosine hydroxylase (TH) expression significantly increased in the MPTP + EE compared to the MPTP + SC group. Finally, expressions of proNGF and p75 neurotrophin receptor (p75(NTR)) were significantly downregulated in the MPTP + EE compared to the MPTP + SC group. Results confirm that EE has neuroprotective effects on dopaminergic neurons via suppression of activation of the p75(NTR)-mediated signaling pathway through the binding of proNGF and p75(NTR). Findings suggest that use of EE as a therapeutic intervention would promote healthy aging by facilitating recovery following brain injury and preventing neurodegenerative diseases.