Sex as a determinant of age-related changes in rat spinal cord inflammation-oxidation state

Abstract

To close the gap in our knowledge of sex influence on age-related changes in inflammation-oxidation state in spinal cord (SC) relevant to inflammation/oxidative-stress associated neuropathologies, 2-3 month-old (young) and 18-20 month-old (old) rats, exhibiting increased level of IL-6, a commonly used marker of inflamm-aging, were examined for inflammatory/redox status, and the underlying regulatory networks' molecules expression. With age, rat SC microglia became sensitized ("primed"), while SC tissue shifted towards mild inflammatory state, with increased levels of proinflammatory IL-1 beta (key marker of microglial systemic inflammation-induced neurotoxicity), which was more prominent in males. This, most likely, reflected age- and sex-related impairment in the expression of CX3CR1, the receptor for fractalkine (CX3CL1), the soluble factor which regulates microglial activation and diminishes production of IL-1 beta (central for fractalkine neuroprotection). Considering that (i) age-related changes in SC IL-1 beta expression were not followed by complementary changes in SC IL-6 expression, and (ii) the reversal in the direction of the sex bias in circulating IL-6 level and SC IL-1 beta expression, it seems obvious that there are tissue-specific differences in the proinflammatory cytokine profile. Additionally, old male rat SC exhibited greater oxidative damage than female, reflecting, most likely, their lower capacity to maintain the pro-oxidant-antioxidant balance. In conclusion, these findings, apart from highlighting the significance of sex for age-associated changes in SC inflammation-oxidation, may be relevant for understating sex differences in human inflammation/oxidative-stress related SC diseases, and consequently, for optimizing their prevention/therapy.