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Amiri A, Janbazi M, Jamali S R, Ehsani vostacolaee S, Shafia S. Impact of Physical Exercise on Behavioral Functions and Neurotrophic Factors on Ovariectomized Rats Exposed to SPS. Res Mol Med (RMM) 2024; 12 (3)
URL: http://rmm.mazums.ac.ir/article-1-586-fa.html

Background: Post-traumatic stress disorder (PTSD) is a severe psychiatric condition associated with anxiety, cognitive deficits, and neurobiological changes. Estrogen deficiency occurs after ovariectomy (OVX) or menopause, exacerbating PTSD symptoms and limiting treatment options. Physical exercise has emerged as a non-pharmacological intervention with neuroprotective effects, but its efficacy under estrogen-deficient conditions remains unclear. This study aimed to evaluate the effects of moderate-intensity forced running wheel (FRW) exercise on PTSD-like behaviors, recognition memory, and neurotrophic factors such as brain-derived neurotrophic factor (BDNF) and insulin-like growth factor 1 (IGF-1) in the hippocampus and prefrontal cortex of ovariectomized rats exposed to single prolonged stress (SPS) as a model of PTSD.

Methods: Adult female Wistar rats (n=7 per group) were allocated to eight groups in a 2×2×2 factorial design based on ovarian status (sham vs OVX), stress exposure (no stress vs SPS), and physical activity (sedentary vs FRW). FRW was performed 30 min/day, 5 days/week for 4 weeks at 10 m/min (~60% VO2 max), indicating moderate intensity. Anxiety-like behaviours (% open arm time [OAT], % open arm entry [OAE]) and recognition memory (discrimination index (DI) were assessed using standard behavioural tests. ELISA was used to measure BDNF and IGF-1 levels in the hippocampus and prefrontal cortex (PFC). Data (Mean±SEM) were analyzed using a three-way ANOVA (OVX × SPS × Exercise) with the Tukey’s post-hoc test; the assumptions of normality and homogeneity were verified. Partial η² and Cohen’s d were reported for omnibus and key pairwise comparisons, respectively (α=0.05, two-tailed).

Results: SPS exposure significantly increased anxiety-like behaviors and impaired recognition memory in both control and ovariectomized rats. FRW exercise ameliorated anxiety and memory deficits and elevated BDNF and IGF-1 levels in control animals under both SPS and non-SPS conditions. However, in ovariectomized rats, the beneficial effects of exercise were confined mainly to non-SPS groups, with limited improvements observed in ovariectomized rats subjected to SPS. Estrogen deficiency diminished the neuroprotective and behavioral benefits of exercise under stress.

Conclusion: Moderate-intensity FRW exercise effectively mitigates PTSD-related behavioral and neurochemical deficits in rats with normal ovarian hormone levels. Still, its efficacy is substantially reduced under estrogen-deficient conditions. These findings highlight the importance of hormonal status in determining the therapeutic potential of exercise for PTSD. Although the SPS model provides valuable insights into PTSD-like symptoms, it does not fully replicate the complexity of human PTSD; therefore, extrapolation to clinical settings should be approached with caution. Combined interventions, including hormonal support, may be more effective for post-menopausal populations.