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

Abstract

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 (p75NTR) 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 p75NTR-mediated signaling pathway through the binding of proNGF and p75NTR. Findings suggest that use of EE as a therapeutic intervention would promote healthy aging by facilitating recovery following brain injury and preventing neurodegenerative diseases.

P75 neurotrophin receptor as a therapeutic target for drug development to treat neurological diseases

“…The p75NTR, encoded by NGFR, was found to play a critical role in the selective neuronal death of dopaminergic neurons in the substantia nigra, as well as in the pathogenesis and progression of PD (Li et al, 2019). One study confirmed that environmental enrichment exerts neuroprotective effects on the survival of dopaminergic neurons through inactivation of the p75NTR-mediated signalling pathway via the binding of proNGF to p75NTR (Cho & Kang, 2020). Another study demonstrated significant increase in p75NTR upregulation following kainic acid insult in the substantia nigra of rat model, suggesting that p75NTR may function importantly in neuronal cell survival or excitotoxic degeneration of dopamine neurons in the substantia nigra in the pathogenesis and development of PD in human beings (Wang et al, 2008).…”

Enriched environment as a nonpharmacological neuroprotective strategy

“…These results indicate that EE could decrease the loss of dopaminergic neuronal cells in the SNpc and striatum. 33 In 6-hydroxydopamine (6-OHDA) PD models, increased cell proliferation has been observed in the SN after EE rearing. 34 In addition, decreased striatal dopaminergic loss and increased expression of cells positive for ionized calcium binding adaptor molecule 1 (Iba-1), nerve antigen 2 (NG2), and glial fibrillary acidic protein (GFAP) were also described.…”

Environmental Enrichment in Cancer as a Possible Tool to Combat Tumor Development: A Systematic Review

“…Eight included studies evaluated tumor volume, which is usually measured using the equation (Volume = length × width 2 × π/6) and expressed in mm 3 and percentage [10,[12][13][14][15][16][17][18]. The results showed that EE was able to significantly reduce tumor volume in mice with colon, melanoma, breast, glioma, pancreatic, liver, and lung cancer.…”