Treadmill Exercise Training Ameliorates Apoptotic Cells and DNA Oxidation in the Cerebral Cortex of Rats Exposed to Chronic Ketamine Abuse.

Moderate-intensity continuous training (MICT) reduces apoptosis and oxidative damage in the cerebral cortex of rats with chronic ketamine abuse. In a study of 24 Wistar rats, those receiving 50 mg/kg/day ketamine for 8 weeks and then undergoing 8 weeks of MICT showed significantly fewer apoptotic cells and lower expression of pro-apoptotic proteins Bax and caspase-3, along with higher anti-apoptotic Bcl-2, compared to rats that only withdrew from ketamine without exercise. MICT also decreased oxidative stress markers (8-oxo-2'-deoxyguanosine) and increased antioxidant enzymes glutathione peroxidase and glutathione reductase, as well as nitric oxide. Levels of malondialdehyde, myeloperoxidase, glutathione, superoxide dismutase, and catalase did not differ between groups. The findings suggest exercise can mitigate ketamine-induced brain damage.

Study at a glance

Abstract

Ketamine abuse damages brain function and structure, increasing reactive oxygen species and apoptosis in the cerebral cortex, but moderate-intensity continuous training (MICT) can enhance antioxidant defences and reduce apoptosis. Therefore, we aimed to answer whether MICT can reduce the side effects of chronic ketamine abuse. 24 Wistar rats were split into control (CON), ketamine abuse (KET), exercise after ketamine withdrawal (KET + EX), and non-intervention ketamine withdrawal (KET + WD) groups. Ketamine intervention groups received 50 mg/kg/day ketamine for 8 weeks; KET + EX underwent 5 MICT sessions/week at 60-75% VO2max for 8 weeks post-withdrawal. Post-sampling of cerebral cortex, we evaluated histological changes, apoptotic cell numbers, Bax, Bcl-2, Caspase-3 mRNA/protein, 8-oxo-2'-deoxyguanosine (OXO) expression, glutathione peroxidase (GPX) and glutathione reductase (GR) mRNA and other oxidative stress and antioxidant markers levels. Effect sizes (ES) were used to assess group differences. MICT significantly reduced apoptotic cells (ES = 14.24, p < 0.0001), decreased Bax and caspase-3 protein expression, and increased Bcl-2 compared to the KET group (Bax: ES = 2.77, p = 0.005; caspase-3: ES = 7.73, p < 0.0001; Bcl-2: ES = 12.11, p < 0.001). It also lowered Bax and caspase-3 mRNA (Bax: ES = 4, p = 0.014; caspase-3: ES = 2.29, p = 0.024). MICT reduced OXO and increased GR and GPX mRNA and nitric oxide (NO) level (GR: ES = 2.02, p = 0.016; GPX: ES = 1.98, p = 0.035; OXO: ES = 11.39, p < 0.0001; NO: ES = 3.52, p = 0.003). Levels of malondialdehyde, myeloperoxidase, glutathione, superoxide dismutase, and catalase remained unchanged between groups. MICT seems effective in reducing apoptosis and oxidative damage in the cerebral cortex of rats with long-term ketamine abuse.