Sex differences in middle-aged and old Wistar rats in response to long-term sulforaphane treatment for prevention of neuroinflammation, cognitive decline and brain senescence.

Abstract

The nervous system (NS) experiences morphological and functional changes during the aging process, where low-grade chronic inflammation, oxidative stress and senescence are key regulators. Sulforaphane (SFN) is an isothiocyanate that activates redox response and inhibits the inflammatory process, which could modify the pro-inflammatory components of senescent cells secretory phenotype (SASP). Here we aimed to determine if SFN long-term treatment was able to prevent age-associated damage in the NS of adult and old females and males Wistar rats. We evaluated cytokines and chemokines profile, senescent cells markers, and memory parameters of adult (15 m.o.) and old (21 m.o.) rats after three months of SFN treatment. Young rats (4 m.o.) were used as age controls. Differences between sexes were observed in the inflammatory profile. Our results showed that SFN-treatment diminished proinflammatory molecules, senescence markers and senescent cells number in brain cortex and hippocampus from males and females' adult rats, but no effects were observed in both sexes old groups compared with the same age control groups. SFN-dependent reduction in inflammatory and senescence parameters resulted in better scores in Barnes Maze Trial memory test when compared with same age non-treated group. Interestingly, adult females showed higher levels of proinflammatory cytokines and chemokines than adult males, which were prevented by SFN-treatment. No effects of SFN were observed in memory of old-treated groups.