Mogrol attenuates lipopolysaccharide (LPS)-induced memory impairment and neuroinflammatory responses in mice.

This study aimed to evaluate whether mogrol, a main bioactive ingredient of Siraitia grosvenorii, could attenuate LPS-induced memory impairment in mice. The behavioral tests and immunohistochemical analysis and Western blot were performed. The present results showed that oral administration of mogrol (20, 40, 80 mg/kg) significantly improved LPS-induced memory impairment in mice. The results also indicated that mogrol treatment significantly reduced the number of Iba1-positive cells, the nuclear NF-κB p65 and levels of TNF-α, IL-1ß and IL-6 both in the hippocampus and frontal cortex of LPS-challenged mice. [Formula: see text].

Montelukast ameliorates streptozotocin-induced cognitive impairment and neurotoxicity in mice.

Extensive studies have demonstrated that neuroinflammation is associated with Alzheimer's disease (AD) and cysteinyl leukotriene receptor 1 (CysLT1R) was involved in neuroinflammation. Montelukast, a highly selective CysLT1R antagonist, has been reported to attenuate learning and memory impairments in the amyloid-ß-induced mouse model of AD. However, whether montelukast also exerts beneficial effects on streptozotocin (STZ)-induced memory deficits in mice is not well known. In the present study, we aimed to investigate the effects of montelukast on STZ-induced cognitive impairment, neuroinflammation and apoptosis in mice. Our data showed that intra-hippocampal microinfusion of STZ resulted in learning and memory impairments, including increased escape latency during acquisition trials and decreased exploratory activities in the probe trial in Morris watermaze (MWM) task, and decreased number of correct choices and increased latency to enter the shock-free compartment in Y-maze test, and caused neuroinflammatory and apoptotic responses, evidenced by increments of nuclear NF-κB p65, TNF-α, IL-1ß, cleaved caspase-3, Bax as well as decreased expression of Bcl-2 in hippocampus. Interestingly, STZ treatment led to up-regulation of protein and mRNA of CysLT1R in hippocampus. Of note, consecutive oral administration of montelukast (1 or 2mg/kg, 3 weeks) remarkably attenuated these effects induced by STZ. However, montelukast had no effect on normal mice. These results suggest that montelukast improves memory impairment and inhibits neuroinflammation and apoptosis in mice exposed to STZ. Montelukast may provide a novel strategy for treating or preventing AD.

PPARδ agonist GW0742 ameliorates Aß1-42-induced hippocampal neurotoxicity in mice.

Amyloid-ß deposition is thought to be associated with memory deficits, neuroinflammation, apoptotic responses, and progressive neuronal death manifested in Alzheimer's disease. Peroxisome proliferator-activated receptor δ (PPARδ) is a transcription factor with potent anti-inflammatory effect. In the current study, the effect of GW0742, a selective PPARδ agonist, on Aß1-42-induced neurotoxicity was investigated in the hippocampus of mice. Intra-hippocampal infusion of aggregated Aß1-42 oligomer (410pmol/mouse) remarkably damaged learning and memory in the Morris water maze (MWM) and Y-maze tests, accompanied by decreased expression of PPARδ in the hippocampus as confirmed by Western blot. Intra-hippocampal infusion of GW0742 (1.06 mM/mouse) significantly improved Aß1-42-induced memory deficits in mice, reversed Aß1-42-induced hippocampal PPARδ down-regulation and repressed Aß1-42-triggered neuroinflammatory and apoptotic responses, indicated by decreased nuclear NF-κB p65, TNF-α, IL-1ß as well as a decrease in cleaved caspase-3 and increased ratio of Bcl-2/Bax in the hippocampus. These results suggest that PPARδ activation ameliorates Aß1-42-induced hippocampal neurotoxicity, and it might play a crucial role in Alzheimer's disease.