The active constituents of Sesamum indicum, sesamin and sesamolin, have already been explored for hypolipidemic action. In this study we have explored the anti-dyslipidemic activity of another active component and metabolite of sesamolin (sesamol), by using acute models of hyperlipidemia viz., a fat tolerance test, a tyloxapol-induced hyperlipidemia model and a chronic model of hyperlipidemia viz., a high-fat diet-induced hyperlipidemia model in Swiss albino mice. Sesamol (100 and 200 mg/kg) significantly (P < 0.05) decreased triacylglycerol absorption in the fat tolerance test by showing a dose-dependent decrease in triacylglycerol levels. The hypolipidemic effect of sesamol at 200 mg/kg was equivalent to 10 mg/kg of orlistat. In the tyloxapol-induced hyperlipidemia model, Sesamol at 200 mg/kg reversed the elevated levels of cholesterol and triacylglycerol compared with the tyloxapol group at 12 and 24 h, which indicates its probable effect on cholesterol synthesis. Chronic hyperlipidemia in mice was produced by feeding a high-diet, a mixture of cholesterol (2 % w/w), cholic acid (1 % w/w) and coconut oil 30 % (v/w) with standard powdered standard animal chow (up to 100 g). Niacin (100 mg/kg) and sesamol (100 mg/kg) significantly (P < 0.05) reduced the elevated body weight compared with the high fat diet control group. Elevated levels of cholesterol and triacylglycerol were significantly (P < 0.05) reversed by the sesamol (50 and 100 mg/kg), implying that it might reduce the absorption and increase the excretion of cholesterol as well.
The radiation fields in space define tangible risks to the health of astronauts, and significant work in rodent models has clearly shown a variety of exposure paradigms to compromise central nervous system (CNS) functionality. Despite our current knowledge, sex differences regarding the risks of space radiation exposure on cognitive function remain poorly understood, which is potentially problematic given that 30% of astronauts are women. While work from us and others have demonstrated pronounced cognitive decrements in male mice exposed to charged particle irradiation, here we show that female mice exhibit significant resistance to adverse neurocognitive effects of space radiation. The present findings indicate that male mice exposed to low doses (≤30 cGy) of energetic (400 MeV/n) helium ions (4He) show significantly higher levels of neuroinflammation and more extensive cognitive deficits than females. Twelve weeks following 4He ion exposure, irradiated male mice demonstrated significant deficits in object and place recognition memory accompanied by activation of microglia, marked upregulation of hippocampal Toll-like receptor 4 (TLR4), and increased expression of the pro-inflammatory marker high mobility group box 1 protein (HMGB1). Additionally, we determined that exposure to 4He ions caused a significant decline in the number of dendritic branch points and total dendritic length along with the hippocampus neurons in female mice. Interestingly, only male mice showed a significant decline of dendritic spine density following irradiation. These data indicate that fundamental differences in inflammatory cascades between male and female mice may drive divergent CNS radiation responses that differentially impact the structural plasticity of neurons and neurocognitive outcomes following cosmic radiation exposure.
Alzheimer's disease (AD) is a progressive neurodegenerative disorder that causes structural as well as functional disturbance to neurons in discrete brain regions. Despite the extensive efforts to understand its pathophysiology, the exact mechanisms underlying AD remain unknown. There are various hypotheses on the causes of AD, including the cholinergic hypothesis, amyloid and tau protein hypothesis, neurovascular hypothesis, mitochondrial mitophagy hypothesis, metal ion hypothesis, and olfactory vector hypothesis (OVH). This article principally aims to provide a general idea of how olfaction is related to cognition and neurodegenerative diseases, particularly AD, and an overview of recent studies in this field. The olfactory system is very well connected to the central brain structure, such as the limbic system, which is associated with olfaction and can lead to evoke strong memories and emotions in human beings. Further, this review tries to reflect the central association of the olfactory system, detailing its anatomical peculiarities to support OVH with evidence on olfactory memory, altered olfactory functions, and memory induced by toxins, thereby culminating in its therapeutic utility through aromas as olfactory agonists. This hypothesis uplifts the role of olfaction and its system from a sensory modality to be an easily accessible point for toxins to reach the brain owing to its anatomical proximity, which eventually becomes a risk factor for neurodegenerative diseases like AD. The major focus of the current review is to specify the distinct involvement of the olfactory system compared to other senses in dementia, particularly AD, both in its pathogenesis and therapy.Funding Information: The authors thank DST-CSRI [New Delhi, India] for financial assistance to conduct the research work on this subject to SNM (Principal investigator) and AR is the recipient of the DST-INSPIRE fellowship.Declaration of Interests: The author’s report no conflict of interest relevant to this work.
Parkinson’s disease (PD) mainly affects the dopaminergic neuronal networks of the substantia nigra, which leads to both motor and nonmotor symptoms of the disease. Based on the reports from the previous studies, 95% of the cases are presented along with olfactory dysfunction. The relevant publications from 2002 to 2021 were searched and shortlisted using PubMed and Google Scholar. In this review, we have discussed the correlation between olfactory dysfunction and PD. Olfactory damage presents earlier than the motor symptoms. Because there are no current methodologies for the early detection of PD, olfactory dysfunction can be used as a potential marker for the early detection of PD and hence paving the way for better therapeutic approaches.
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