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Published on: January 22, 2016
Exercise-mediated modulation of hippocampal apoptotic gene expression and behavioral outcomes in
Shima Ababzadeh1,2, Hamid Reza Salimi3, Mohsen Eslami Farsani1,4
1Cellular and Molecular Research Center, Faculty of Medical Sciences, Qom University of Medical Sciences, Qom, Iran.
Purpose:
Methamphetamine (MA) abuse causes significant neurotoxicity, with limited pharmacological options available to mitigate cognitive deficits. This study investigated whether moderate-intensity aerobic training (MIAT) reduces hippocampal apoptosis and improves cognitive function in MA-exposed rats.
Methods:
Forty male rats were randomly assigned to four groups (Saline, MA, MA + MIAT, and MIAT) and given increasing MA doses (2.5-10 mg/kg) over 23 days. For six consecutive weeks, the rats in the MIAT groups underwent daily aerobic sessions (six days per week). Cognitive function was assessed via a passive avoidance test in a shuttle box for learning and memory assessment. Hippocampal markers of oxidative stress and the expression of apoptosis-related genes (Bcl-2, Bax, and TGF-β) were quantified via biochemical assays and qPCR, respectively.
Results:
Compared with saline, MA administration significantly impaired learning and memory, increasing the number of dark compartment entries (p < 0.0001). Aerobic training reversed these deficits by reducing entries and enhancing latency. Furthermore, MA increased hippocampal MDA levels and suppressed TAC (p < 0.0001), whereas exercise restored the oxidative balance. Gene expression analysis revealed MA-mediated upregulation of Bax and TGF-β, alongside decreased Bcl-2 (p < 0.0001), which were normalized by aerobic training.
Conclusion:
This study revealed that MIAT mitigated MA-induced cognitive deficits, oxidative stress, and apoptotic gene dysregulation in rats. Exercise normalized Bax, Bcl-2, and TGF-β expression; restored antioxidant levels and memory; and may be a clinically relevant, noninvasive intervention to support cognitive recovery in MA-exposed individuals.

