Environmental Enrichment Attenuates Oxidative Stress and Alters Detoxifying Enzymes in an A53T α-Synuclein Transgenic Mouse Model of Parkinson’s Disease

Abstract

Although environmental enrichment (EE) is known to reduce oxidative stress in Parkinson’s disease (PD), the metabolic alternations for detoxifying endogenous and xenobiotic compounds according to various brain regions are not fully elucidated yet. This study aimed to further understand the role of EE on detoxifying enzymes, especially those participating in phase I of metabolism, by investigating the levels of enzymes in various brain regions such as the olfactory bulb, brain stem, frontal cortex, and striatum. Eight-month-old transgenic PD mice with the overexpression of human A53T α-synuclein and wild-type mice were randomly allocated to either standard cage condition or EE for 2 months. At 10 months of age, the expression of detoxifying enzymes was evaluated and compared with wild-type of the same age raised in standard cages. EE improved neurobehavioral outcomes such as olfactory and motor function in PD mice. EE-treated mice showed that oxidative stress was attenuated in the olfactory bulb, brain stem, and frontal cortex. EE also reduced apoptosis and induced cell proliferation in the subventricular zone of PD mice. The overexpression of detoxifying enzymes was observed in the olfactory bulb and brain stem of PD mice, which was ameliorated by EE. These findings were not apparent in the other experimental regions. These results suggest the stage of PD pathogenesis may differ according to brain region, and that EE has a protective effect on the PD pathogenesis by decreasing oxidative stress.

Environmental Enrichment and Metformin Improve Metabolic Functions, Hippocampal Neuron Survival, and Hippocampal-Dependent Memory in High-Fat/High-Sucrose Diet-Induced Type 2 Diabetic Rats

“…The detoxifying metabolism has three phases that modify toxins into active metabolites, catalyze the active metabolites into hydrophilic products with transferase enzymes, and excrete the final products via various transporter systems. The EE regulates enzymes participating in the detoxification metabolism, such as cytochrome P450 family 1 subfamily A member 2 (Cyp1a2) and carbonyl reductase2 (Cbr2) [ 40 ]. The anti-oxidative activities of EE and metformin might be responsible for anti-diabetic and neuroprotective effects in the HFS diet-induced T2D rats.…”

Adiponectin/AdiopR1 signaling prevents mitochondrial dysfunction and oxidative injury after traumatic brain injury in a SIRT3 dependent manner

“…In the wire hanging test [ 54 ], a metal wire (50 cm) was stretched between two posts and suspended 50 cm above the ground. Mice were guided to grasp the wire with their forelimbs.…”

Impact of Fatty Acid-Binding Proteins in α-Synuclein-Induced Mitochondrial Injury in Synucleinopathy

“…In contrast, α-synuclein translocated to the mitochondria in response to cellular stress and directly upon intracellular acidification [ 142 ], dysregulation of ion transport [ 143 ], hydrolysis of high-energy nucleotides [ 144 ], and the PD toxin MPP + impaired cellular energy metabolism and resulted in a decrease in pH [ 145 ]. The mutant α-synuclein-like A53T is more prone to aggregation, attenuates oxidative stress [ 146 , 147 ], and interferes with iron homeostasis [ 148 , 149 ]. Inhibition of α-synuclein aggregation is important for maintaining iron homeostasis and normal ROS and pH levels, thereby protecting the mitochondria from α-synuclein toxicity in neurodegeneration.…”