Impact of Chronic Mild Stress on Neurotrophic and Hypothalamic-Pituitary-Adrenal Factors in the Brain of Rats Submitted to Sepsis

The present study aimed to investigate the effects of chronic mild stress (CMS) on neurotrophic factors in the brains of rats subjected to the cecal ligation and puncture (CLP) model of sepsis. After 30 days of the CLP procedure, the animals were subjected to CMS. Twenty-four hours after the last stressor, the animals were euthanized, their blood was collected, and their brains were dissected in the frontal cortex and hippocampus. Then, the levels of brain-derived neurotrophic factor, neurotrophin-3, neurotrophin-4, nerve growth factor, and glial cell line-derived neurotrophic factor were evaluated in the brain structures. The levels of adrenocorticotropic hormone and corticosterone were evaluated in the serum of the rats. The four experimental groups of the present study were: (1) Sham + Non-stressed; (2) Sepsis + Non-stressed; (3) Sham + CMS; (4) Sepsis + CMS. CMS increased adrenocorticotropic hormone and corticosterone levels, whereas sepsis alone did not significantly alter these hormones. Regarding neurotrophic factors, CMS reduced the levels of BDNF, NT-3, NT-4, and NGF in both the hippocampus and frontal cortex, regardless of prior sepsis exposure. Sepsis alone was also associated with reduced levels of these neurotrophins, although the magnitude of the effect varied depending on the specific neurotrophin and brain region, with greater reductions observed for BDNF and NGF. No interaction between sepsis and CMS was detected for these neurotrophins, suggesting independent effects. Our findings suggest that sepsis and CMS independently affect most neurotrophin levels, with no clear evidence that prior sepsis potentiates the effects of subsequent CMS. GDNF represents an exception, pointing to potential region-specific mechanisms that warrant further investigation.