The effect of voluntary wheel running on natural killer cell cytotoxicity after olfactory bulbectomy
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This dissertation summarized and quantitatively evaluated the published literature on the effect of exercise on natural killer (NK) cell cytotoxic function in humans using meta-analysis. It, also investigated the putative role of exercise in the modulation of splenic NK cell cytotoxicity after olfactory bulbectomy (OBX), a rat model of human depression which has immunosuppressive features. Results from a quantitative synthesis of the literature in humans indicated that there were moderate effects of acute exercise and exercise training and a large effect of fitness/training status on NK cell cytotoxicity. Moderator analyses showed that acute exercise produced a distinct pattern of alteration in NK cell cytotoxicity. NK cell cytotoxicity is markedly increased during and soon after exercise, decreased below the pre-exercise baseline 1-3 hours after termination of exercise, and returned to the baseline value within 24 hours of recovery. Also, effects of acute exercise were larger for sedentary or female participants and when an exercise session lasted 20 minutes to 2 hours, compared to exercise sessions that were longer than 2 hours. Therefore, the synthesis of literature on the effect of exercise on NK cell activity revealed that NK cell activity is influenced by both acute exercise and exercise training, but this effect varied according to characteristics of the exercise and participants. The effects of OBX on splenic NK cell cytotoxicity in vitro, plasma corticosterone level and NK cell apoptosis in Long-Evans rats were examined. Whether activity wheel running and imipramine would moderate those effects also was examined. A 2 Condition (OBX vs. sham) x 2 Group (activity wheel vs. sedentary) x 2 Treatment (imipramine vs. saline) factorial design was used. Male Long-Evans rats were randomly assigned to groups 24 hours after OBX or sham surgery. After 3 weeks, animals were tested for open-field behavior. Blood and spleens were collected 24-72 hours later and assayed for NK cell cytotoxicity using standard chromium release and for plasma corticosterone using radioimmunoassay. Analysis of NK cell apoptosis was done by flow cytometry. Incubation with dexamethasone (100 nM ) resulted in apoptosis of NK cells as expected. NK cell activity was not affected by OBX or 3 weeks of voluntary wheel running or imipramine. Also, there was no difference in the percentage of apoptotic cells between OBX (4.58 ± 3.69 %) and sham (4.93 ± 5.09 %) animals. In contrast to expected results, plasma corticosterone level was lower in OBX rats (6.52 ± 6.0 µg/dL) compared to sham surgery animals (10.30 ± 8.70 µg/dL), p = 0.03. Although olfactory bulbectomy resulted in hyperactive behavior, it did not result in immunosuppression of splenic NK cell activity through the hypothesized mechanism of glucocorticoid-induced cell apoptosis.