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-1β (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-1β (central for fractalkine neuroprotection). Considering that (i) age-related changes in SC IL-1β 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-1β 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.

Molecular changes associated with spinal cord aging

“…Previous studies have reported an increase in proinflammatory cytokines and glial activation in aging brain, as well as in rat spinal cord (Sparkman and Johnson 2008;Xie et al 2013;Galbavy et al 2017;Nacka-Aleksić et al 2017). We were interested in determining, whether there was an increase in inflammation in spinal cord from aging mice.…”

Contrast-enhanced ultrasound imaging detects anatomical and functional changes in rat cervical spine microvasculature with normal aging

“…The current study is also limited by the subject demographics; we only used male rats, and we only examined adult and aged animals. Sex is a critically relevant biological variable for the response to spinal cord injury in normal adults and has been implicated in differences in spinal cord inflammation and gene expression with normal aging (48, 49). Age-dependent changes may occur in a progressive or stepwise manner, necessitating further study with young, middle aged, and aged cohorts.…”

Sex-specific remodeling of T-cell compartment with aging: Implications for rat susceptibility to central nervous system autoimmune diseases

“…3). Notably, age-related "priming" of microglia was shown to be brain region-and sex-specific [22,[284][285][286][287]. In the rat it is shown to be strain-specific, as well [13].…”