Expression Of Bcl-2 In Hippocampus Research Articles

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-β-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-1β, 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.

Therapeutic Hypothermia Enhances Cold-Inducible RNA-Binding Protein Expression and Inhibits Mitochondrial Apoptosis in a Rat Model of Cardiac Arrest.

Therapeutic hypothermia is well known for its protective effect against brain injury after cardiac arrest, but the exact mechanism remains unclear. Cold-inducible RNA-binding protein (CIRP), a member of cold shock protein, enables mammalian cells to withstand decreased temperature by regulating gene translation. However, the role of CIRP in global cerebral ischemia after therapeutic hypothermia has not been clearly elucidated. In the present study, rats resuscitated from 4min of cardiac arrest were separately treated with therapeutic hypothermia (immediately after return of spontaneous circulation (ROSC); targeted temperature at 33°C) and therapeutic normothermia (targeted temperature at 36.8°C) for 6h. The hippocampus was harvested at 0h (baseline), 6h, 12h, 1day, 3days, and 7days after ROSC. The expression of CIRP messenger RNA (mRNA) was assessed by real-time PCR. CIRP and mitochondrial apoptosis-associated proteins were tested by Western blot. The histological changes and neurological function were respectively evaluated by hematoxylin-eosin staining and neurological deficit score (NDS). Compared with baseline, rats resuscitated from cardiac arrest showed increased expression of CIRP, Bax, Caspase 9, and Caspase 3 and decreased expression of Bcl-2 in hippocampus (P < 0.05). However, therapeutic hypothermia after ROSC alleviated the alterations of Bax, Caspase 9, Caspase 3, and Bcl-2, while further increased the hippocampal expression of CIRP mRNA and protein, when compared with the normothermia rats (P < 0.05). In addition, compared with the therapeutic normothermia rats, histopathological damage in CA1 zone and NDS were respectively decreased and increased in the hypothermia rats (P < 0.05). Our findings suggest that 32°C therapeutic hypothermia exerts an important neuroprotective effects by up-regulating CIRP expression and inhibiting mitochondrial apoptosis factor production in the cardiac arrest rat model.