Changes in serotonin levels with age could affect stress responses in the brain

Natural changes in bodily hormones as a result of increasing age can have effects on the functioning of both body and mind. It has been suggested that gradual changes in hormones such as serotonin could play a large part in cardiovascular diseases, depression and other mood disorders. Diminished levels of serotonin have long been linked to depression. Evidence shows that the amygdala, the area of the brain which controls emotions, can be affected by varying levels of serotonin. Researchers have observed that increased levels of serotonin cause the brain to process emotionally-charged information in a more positive way, thus decreasing negative thought processes. This results in an overall positive mood of a depressed person by way of responding to emotion-based stimuli in a more favorable light (P.J. Cowen and M. Browning, 2015).

Dr. Yamaguchi and colleagues (2016) from Aichi Medical University and Kochi University tested the effects of stressors on tryptophan hydroxylase (TPH) expression in the brain, specifically the dorsal raphe nucleus (DRN), over the lifetime of rats. TPH is the rate-limiting enzyme in the synthesis of serotonin. Stress exposure can affect the growth of the hypothalamic-pituitary-adrenocortical (HPA) axis, causing organizational changes that alter one’s emotional functioning and response to stress. The researchers determined that certain stressors, such as neonatal maternal separation, result in cognitive and behavioral effects that persist even through old age.

The DRN is a section of the brain located on the brainstem. The DRN can be further subdivided into the dorsal, ventral and lateral areas. The dorsal and ventral areas have links to other regions of the brain, such as the frontal cortex and amygdala, which dictate stress and anxiety responses. Neurons in the DRN also release serotonin, which is a target hormone for drugs that treat depression (Y. Li et al., 2016). Serotonin has a known effect in the regulation of stress responses in the brain, and serotonergic function is partly regulated by estrogen in both males and females. In female rat brain, estrogen levels increase with exposure to stress. In males, testosterone is converted to estradiol by aromatase. Since testosterone concentrations have been shown to decrease with age, it is likely that endogenous estrogen concentrations in the brain subsequently decrease, and stress responses are altered.

In this study, researchers used young male rats (age 7 weeks), old male rats (age 20 months) and old female rats (age 20 months), to which varying stress-related conditions were assigned. Some experimental groups experienced unpredictable stress at unpredictable times of day. For one male experimental group that was subjected to stressful conditions at both young and old age, they received restraint stress consistently. Restraint stress was performed in methods similar to that of a past study by some of the same researchers (N. Yamaguchi et al., 2010).

Enzo’s Testosterone ELISA kit was used to measure rat plasma samples in both young and old rats, some of who were stressed and some who were not. These enzyme immunoassays revealed no significant variations in stress exposure, or in interactions of age and stress exposure in these rats. There was a significant variation, however, in the effect of age on testosterone levels when comparing that of the young rats (age 8-12 weeks) to that of aged rats (20-24 months). Altogether, these results suggest that stress response can change with age and that aging in male rats increases TPH levels in the DRN, leading to plateau effects which prevent further TPH expression upon stress exposure. Further studies are necessary to determine the physiological effects of these endocrine changes.

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