Reproductive aging in females is characterized by a progressive decline in fertility that begins at birth and extends through the perimenopausal transition. A decline in estrogen concentrations during this transitory period lowers the activity of serotonin; a known neurotransmitter which has been well established to ultimately improve mental health status. Thus, this study aimed to assess ovarian serotonin mRNA receptors; its central and peripheral levels interplay at diestrus phase of the estrous cycle in perimenopausal rats subjected to standard exercise regimen.

Female immature Wistar rats (postnatal day [PND] 21) were housed in groups of seven per cage (n = 7) and randomly divided into three major groups (Control, VCD, and Aging). At PND 28, Control rats were injected with Corn oil (2.5uL/kg BW) for 15 days; VCD rats were injected with 4-Vinylcyclohexene diepoxide (160mg/kg BW) diluted in Corn oil (2.5uL/kg BW) for 15 days; naturally Aging rats 180 days old (no injection of VCD or Corn oil) were used as aged rats. Fifty (50) days after corn oil/VCD injection and 230 days in Aging rats, animals were further sub-divided into 2 groups; exercise (subjected to exercise regimen of 1 hour duration 3 times weekly on a treadmill for 3 weeks) and non-exercise group. On diestrus morning after the exercise regimen, animals were humanely sacrificed, prefrontal cortex (PFC) and hippocampus (HIPPO) were removed on ice and homogenized; and cardiac puncture was carried out to collect blood (serum) for measurement of peripheral serotonin levels using specialized ELISA kits. Both ovaries were quickly removed and placed in RNA later fluid for storage until serotonin mRNA analysis using standard mRNA extraction and RT-qPCR techniques. Data was analyzed using One-way ANOVA followed by a Bonferroni post hoc test using GraphPad Prism 7 software.

Serum serotonin (ng/ml) was significantly higher (p<0.05) in Aging rats (45.61±6.72) compared to Control (19.45±2.80) and VCD (20.90±2.30). Exercise significantly reduced (p<0.05) serum serotonin in VCD (14.62±1.13ng/ml) and Aging rats (26.72±5.71) compared to Control (23.52±1.83). In PFC, serotonin (ng/ml) in Aging rats (3.41±0.31) was significantly lower (p<0.05) compared to Control (5.91±0.60) and VCD (6.90±0.90) rats. Exercise significantly increased (p<0.05) serotonin in Aging rats (6.99±1.04) compared to Control (5.79±0.83) and VCD (8.01±0.71). In HIPPO, there were no significant changes observed across the groups. In the ovaries, 5-HT₁ receptors were significantly reduced (p<0.05) in Aging rats (4.33±0.43) compared to VCD (9.63±0.82) rats only [Control was (4.60±1.58)]. Exercise significantly reduced (p<0.05) 5-HT₁ receptors (6.41±0.95) in VCD rats; while significantly increasing it (p<0.05) in Aging rats (8.04±1.69), and no significant difference in Control rats (5.97±1.33). The 5-HT₂ receptors in ovaries, were significantly lowered (p<0.05) in VCD (2.27±0.49) and Aging (2.81±0.56) compared to Control (5.20±1.23). Exercise significantly increased (p<0.05) 5-HT₂ receptors in Aging (5.91±1.57), Control (8.32±1.37) and VCD (4.23±1.41) rats.

Exercise seems beneficial in improving mental health during perimenopausal transitory period by enhancing central, peripheral and ovarian serotonin interplay.