Effect of rapamycin on repeated immobilization stress-induced immune alterations in the rat spleen.

Chronic stress modulates immune system functions via neuroendocrine pathways. Rapamycin inhibits activity of immune cells through the mTOR signaling pathway. We investigated the effect of rapamycin (15 mg/kg, 3-times/week) on neuroimmune-endocrine system in the spleen of rats exposed to 42 cycles of 2-h immobilization. Rapamycin enhanced the activity of hypothalamic-pituitary-adrenocortical axis induced by stress exposure, prevented stress-induced expression of natural killer cell markers while reversed stress-evoked decline of Th2 immune response markers. Overall, our findings suggest that rapamycin may act on immune functions not only directly by inhibiting of mTOR in immune cells but also indirectly via modulation of neuroendocrine system.

Exposure to a single immobilization or lipopolysaccharide challenge increases expression of genes implicated in the development of Alzheimer's disease in the mice brain cortex.

OBJECTIVES: Despite extensive research efforts, mechanisms participating on development of Alzheimer's disease (AD) are covered only partially. Data from the last decades indicate that various stressors, as etiological factors, may play a role of in the AD. Therefore, we investigated the effect of two acute stressors, immobilization (IMO) and lipopolysaccharide (LPS), on the AD-related neuropathology. METHODS: Adult C57BL/6J mice males were exposed to a single IMO stress or a single intraperitoneal injection of LPS (250 µg/kg body weight). After terminating the experiments, the brains were removed and their cortices isolated. Gene expression of pro-inflammatory cytokines, as well as expression of genes implicated in the AD neuropathology were determined. In addition, mediators related to the activation of the microglia, monocytes, and perivascular macrophages were determined in brain cortices, as well. RESULTS: In comparison with the control animals, we found increased gene expression of proinflammatory mediators in mice brain cortex in both IMO and LPS groups. In stressed animals, we also showed an increased expression of genes related to the AD neuropathology, as well as positive correlations between genes implicated in AD development and associated neuroinflammation. CONCLUSIONS: Our data indicate that acute exposure to a strong IMO stressor, composed of the combined physical and psychological challenges, induces similar inflammatory and other ADrelated neuropathological changes as the immune LPS treatment. Our data also indicate that cytokines are most likely released from the peripheral immune cells, as we detected myeloid cells activity, without any microglia response. We hypothesize that stress induces innate immune response in the brain that consequently potentiate the expression of genes implicated in the AD-related neuropathology.