Sulforaphane-induced NRF2 activation improves spatial memory and modulates neuroinflammation in a streptozotocin-induced rat model of sporadic Alzheimer’s disease

Alzheimer’s disease (AD) is characterized by cognitive decline and sleep dysregulations. Nuclear factor erythroid 2–related factor2 (NRF2) regulates antioxidant and cytoprotective pathways. Its contribution to sporadic AD associated behavioural, and sleep abnormalities remains unclear. In this study, adult male Wistar rats ( n = 24) were divided into four groups ( n = 6/group): Control+vehicle, Control + SFN, STZ-induced sporadic AD+vehicle, and AD + SFN. Control and AD model were developed by intracerebroventricular administration of artificial cerebrospinal fluid and Streptozotocin (3 mg/kg). SFN dosage was 10 mg/Kg, i.p., single-dose/day for 11 days. Elevated plus maze and Barnes maze were conducted. NLRP3, TNFα, Iba1, GFAP, and hypothalamic NRF2 were assessed by immunohistochemistry, whereas hippocampal NRF2, NF-κB, and PSD95 were further validated by Western blotting. Hippocampal micromineral levels were quantified using ICP-MS. Sleep architecture was quantified using EEG, EOG, and EMG recordings. SFN treatment significantly improved time spent in open arms and reduced escape box latency in STZ-treated rats. NRF2 expression was enhanced in hippocampus and hypothalamus, accompanied by increased PSD95 levels and attenuated NLRP3, NF-κB, and TNFα expression. SFN decreased activated microglia and partially normalized hippocampal micromineral homeostasis. SFN significantly improved NREM and REM sleep duration, shortening REM latency. NRF2 activation by sulforaphane attenuates cognitive deficits and sleep architecture disruptions in AD.