Responses of hypothalamic orexin-containing neurons to cyclophosphamide, EHF-irradiation of the skin, and their combination in rats

Orexins are neuromediators that participate in the regulation of feeding behavior, energy metabolism, circadian rhythms and perception of pain. The aim of the present study was to clarify the responses of the hypothalamic orexin-containing neurons to an intraperitoneal injection of cyclophosphamide (CPA), extremely high frequency (EHF)-electromagnetic stimulation of skin, which is used to modulate side effects of cytostatics and their combination.The activation of orexin-containing neurons was determined by recording of the intensity of c-Fos protein expression. Injection of cyclophosphamide (40 mg/kg) or EHF-irradiation of the skin decreased the staining of orexin-containing neurons, which was most pronounced in the subfornical region of the lateral hypothalamic area (LHAs). A redistribution of orexin from the perinuclear space to the processes of these cells took place, which occurs after the activation and the expression of the c-fos-gene. c-Fos protein was expressed in most neurons with minimum content of orexin, i.e. activation of these neurons correlated with the redistribution of orexins caused by skin EHF-irradiation and injection of cyclophosphamide (CPA). EHF-irradiation of the skin before and after injection of CPA increased the staining of orexin-containing neurons, i.e. it prevented the redistribution of orexin.