DOI: https://doi.org/10.2478/acph-2026-0009
Article ID: 260009 (18 pages)
Acta Pharm. 76(1) (2026)
Article
H3 relaxin mediated neuroprotection in Alzheimer’s disease pathology induced by streptozotocin in mouse models: Impact on memory improvement, autophagy and PI3K/Akt-mTOR signalling pathway
HUIYU ZHAO, YUHONG SUN, SHAIK ALTHAF HUSSAIN, HUA GAO
Abstract
Alzheimer's disease (AD) is characterised by β-amyloid (Aβ) plaque accumulation and tau hyperphosphorylation. H3 relaxin, a neuropeptide, is known to exert neuroprotective effects. In this study, we investigated how H3 relaxin confers neuroprotection in a streptozotocin (STZ)-induced mouse model and modulates PI3K/Akt-mTOR signalling. Mice were divided into four groups (n = 6 per group): control (saline), STZ, STZ + H3 relaxin, and STZ + donepezil. Following STZ induction, H3 relaxin (1 µg per day) was administered intracerebroventricularly (ICV) for 14 consecutive days, whereas donepezil (2.5 mg kg–1 per day) was administered orally for the same duration. Cognitive performance was assessed using the Morris water maze (MWM) test. Aβ deposition in the cortex was evaluated through immunohistochemistry. Western blotting was conducted for tau phosphorylation, PI3K/Akt/mTOR signalling, and autophagy markers in the hippocampus. Oxidative stress and inflammation markers were measured using ELISA. H3 relaxin markedly improved memory by decreasing escape latency and duration while spending more time in the target quadrant in the MWM test. Additionally, H3 relaxin reduced Aβ plaque burden and tau phosphorylation (Ser396/404) while enhancing PI3K/Akt-mTOR signalling. Oxidative stress was attenuated, as evidenced by increased GSH and HO-1 levels and reduced MDA and H2O2 concentrations. Moreover, markers of inflammation, NF-κB and TNF-α were suppressed. Overall, H3 relaxin ameliorated cognitive deficits in STZ-induced AD mice through modulation of impaired PI3K/Akt-mTOR signalling, reduction of Aβ and tau pathology, and promotion of autophagy.
Keywords
Alzheimer disease, streptozotocin, H3 relaxin, neuroprotection, memory improvement
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