Sesamin: Insights into its protective effects against lead-induced learning and memory deficits in rats.

BACKGROUND: Lead (Pb) is one of the most hazardous pollutants that induce a wide spectrum of neurological changes such as learning and memory deficits. Sesamin, a phytonutrient of the lignan class, exhibits anti-inflammatory, anti-apoptotic, and neuroprotective properties. The present study was designed to investigate the effects of sesamin against Pb-induced learning and memory deficits, disruption of hippocampal theta and gamma rhythms, inflammatory response, inhibition of blood δ-aminolevulinic acid dehydratase (δ-ALA-D) activity, Pb accumulation, and neuronal loss in rats. METHODS: Sesamin treatment (30 mg/kg/day; P.O.) was started simultaneously with Pb acetate exposure (500 ppm in standard drinking water) in rats, and they continued for eight consecutive weeks. RESULTS: The results showed that chronic exposure to Pb disrupted the learning and memory functions in both passive-avoidance and water-maze tests, which was accompanied by increase in spectral theta power and theta/gamma ratio, and a decrease in spectral gamma power in the hippocampus. Additionally, Pb exposure resulted in an enhanced tumor necrosis factor-alpha (TNF-α) content, decreased interleukin-10 (IL-10) production, inhibited blood δ-ALA-D activity, increased Pb accumulation, and neuronal loss of rats. In contrast, sesamin treatment improved all the above-mentioned Pb-induced pathological changes. CONCLUSION: This data suggests that sesamin could improve Pb-induced learning and memory deficits, possibly through amelioration of hippocampal theta and gamma rhythms, modulation of inflammatory status, restoration of the blood δ-ALA-D activity, reduction of Pb accumulation in the blood and the brain tissues, and prevention of neuronal loss.

Ellagic acid protects against diabetes-associated behavioral deficits in rats: Possible involved mechanisms.

AIMS: Diabetes mellitus (DM), a chronic metabolic disease, is associated with behavioral deficits. It has been suggested that ellagic acid (EA), a natural polyphenol compound, has potent anti-diabetic, anti-inflammatory, and neuroprotective properties. The present study was aimed to explore the potential protective effects of EA against diabetes-associated behavioral deficits and verified possible involved mechanisms. MAIN METHODS: Fifty adult male Wistar rats were randomly divided into five groups: i.e., CON: normal rats treated with vehicle (5 ml/kg/day; P.O.), EA: normal rats treated with EA (50 mg/kg/day; P.O.), STZ: diabetic rats treated with vehicle (5 ml/kg/day; P.O.), STZ + INS: diabetic rats treated with insulin (6 IU/rat/day; S.C.), STZ + EA: diabetic rats treated with EA (50 mg/kg/day; P.O.). All the groups were under treatment for eight consecutive weeks. During the seventh and eighth weeks, behavioral functions of the rats were assessed by commonly used behavioral tests. Subsequently, pro- and anti-inflammatory cytokines, neurotrophic factors, and also histological changes were evaluated in both cerebral cortex and hippocampus of the rats. KEY FINDINGS: Chronic EA treatment attenuated anxiety/depression-like behaviors, improved exploratory/locomotor activities, and ameliorated cognitive deficits in diabetic rats. These results were accompanied by decreased blood glucose levels, modulation of inflammation status, improved neurotrophic support, and amelioration of neuronal loss in diabetic rats. In some aspects, treatment with EA was even more effective than insulin therapy. SIGNIFICANCE: The current work's data confirms that EA could potentially serve as a novel, promising, and accessible protective agent against diabetes-associated behavioral deficits, owing to its anti-hyperglycemic, anti-inflammatory, and neurotrophic properties.

Memory deficits and hippocampal inflammation in cerebral hypoperfusion and reperfusion in male rats: Neuroprotective role of vanillic acid.

Ischemic stroke is one of the leading causes of neurological deterioration and mortality worldwide. Neuroprotective strategies are being investigated to minimize cognitive deficits after ischemic events. Here we investigated the neuroprotective potential of vanillic acid (VA) in an animal model of transient bilateral common carotid artery occlusion and reperfusion (BCCAO/R). Adult male Wistar rats (250-300 g) were randomly divided in 4 groups and submitted to either cerebral hypoperfusion-reperfusion or a sham surgery after two-weeks of pretreatment with VA and/or normal saline. To induce the animal model of hypoperfusion, bilateral common carotid arteries were occluded (2VO model) for 30 min, followed by 72 h of reperfusion. Subsequently, their cognitive performance was evaluated in a Morris water maze (MWM) test, and also hippocampi were removed for ELISA assays and TUNEL staining test. The results showed that 2VO significantly reduced the spatial memory performance in MWM. As well as, BCCAO/R increased the level of IL-6, TNF-α and TUNEL positive cells, and also decreased the contents of IL-10 in the hippocampus of vehicle- pretreated groups as compared to the sham-operated groups. Furthermore, 14 consecutive days pretreatment with VA significantly restored the spatial memory, decreased the levels of IL-6, TNF-α and TUNEL positive cells and also increased the IL-10 levels in the hippocampi of the BCCAO/R rats. VA alone did not show any change neither in the status of various cytokines nor behavioral and TUNEL staining tests over sham values. Our data confirm that VA could potentially serve as a novel, promising, and accessible neuroprotective agent against cerebrovascular insufficiency states and vascular dementia.