SEW2871 reduces seizures via the sphingosine 1-phosphate receptor-1 pathway in the pentylenetetrazol and phenobarbitone kindling model of drug-refractory epilepsy.

Epilepsy is a prevalent neurological disorder characterized by neuronal hypersynchronous discharge in the brain, leading to central nervous system (CNS) dysfunction. Despite the availability of anti-epileptic drugs (AEDs), resistance to AEDs is the greatest challenge in treating epilepsy. The role of sphingosine-1-phosphate-receptor 1 (S1PR1) in drug-resistant epilepsy is unexplored. This study investigated the effects of SEW2871, a potent S1PR1 agonist, on a phenobarbitone (PHB)-resistant pentylenetetrazol (PTZ)-kindled Wistar rat model. We measured the messenger ribonucleic acid (mRNA) expression of multi-drug resistance 1 (MDR1) and multi-drug resistance protein 5 (MRP5) as indicators for drug resistance. Rats received PHB + PTZ for 62 days to develop a drug-resistant epilepsy model. From day 48, SEW2871 (0.25, 0.5, 0.75 mg/kg, intraperitoneally [i.p.]) was administered for 14 days. Seizure scoring, behaviour, oxidative markers like reduced glutathione, catalase, superoxide dismutase, inflammatory markers like interleukin 1 beta tumour necrosis factor alpha, interferon gamma and mRNA expression (MDR1 and MRP5) were assessed, and histopathological assessments were conducted. SEW2871 demonstrated dose-dependent improvements in seizure scoring and neurobehavioral parameters with a reduction in oxidative and inflammation-induced neuronal damage. The S1PR1 agonist also downregulated MDR1 and MRP5 gene expression and significantly decreased the number of dark-stained pyknotic nuclei and increased cell density with neuronal rearrangement in the rat brain hippocampus. These findings suggest that SEW2871 might ameliorate epileptic symptoms by modulating drug resistance through downregulation of MDR1 and MRP5 gene expression.

A Review on Natural Antioxidants for Their Role in the Treatment of Parkinson's Disease.

The neurodegenerative condition known as Parkinson's disease (PD) is brought on by the depletion of dopaminergic neurons in the basal ganglia, which is the brain region that controls body movement. PD occurs due to many factors, from which one of the acknowledged effects of oxidative stress is pathogenic pathways that play a role in the development of Parkinson's disease. Antioxidants, including flavonoids, vitamins E and C, and polyphenolic substances, help to reduce the oxidative stress brought on by free radicals. Consequently, this lowers the risk of neurodegenerative disorders in the long term. Although there is currently no cure for neurodegenerative illnesses, these conditions can be controlled. The treatment of this disease lessens its symptoms, which helps to preserve the patient's quality of life. Therefore, the use of naturally occurring antioxidants, such as polyphenols, which may be obtained through food or nutritional supplements and have a variety of positive effects, has emerged as an appealing alternative management strategy. This article will examine the extent of knowledge about antioxidants in the treatment of neurodegenerative illnesses, as well as future directions for research. Additionally, an evaluation of the value of antioxidants as neuroprotective agents will be provided.

"Heart strings and purse strings" revisited: A preregistered replication and extension.

The Appraisal-Tendency Framework outlines that discrete emotions of similar valence behave differently, based on each emotion's specific appraisal profile. In the domain of pricing decisions, a seminal paper by Lerner and colleagues report incidental, negative emotions of disgust and sadness to show a divergent effect on spending decisions based on the perceived ownership of a commodity. Specifically, disgust-reduced spending while sadness increased spending on a new product. However, these researchers theorized, but did not statistically test the effects of emotion-induced motivational goals for sadness ("change circumstances") and disgust ("expel and avoid") as the drivers behind their divergent effects on spending. This study (N = 403) sought to replicate these primary findings in close adherence to the original protocol with better measurement properties in a different geographical location. It further extended the examination by empirically testing the distinct mediating processes for sadness and disgust by utilizing measures identified from a pilot study (N = 169) based on the original protocol. We found support for the effect of sadness (vs. disgust and neutral) in inducing higher choice prices through the motivational goal of changing circumstances, but the expected pattern of results for disgust was not replicated. Additionally, we examined the role of arousal in this context as a factor driving the effect of these emotions on spending. Our research offers new insights regarding the well-known "misery-is not miserly" effect for practitioners while also providing impetus for future research on the endowment effect. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Geographically varying effects of weather on tobacco consumption: implications for health marketing initiatives.

Weather and its fluctuations have been found to influence the consumption of negative hedonic goods. However, such findings are of limited use to health marketers who cannot control the weather, and hence, its effects. The current research utilizes data obtained at the zip-code level to study geographical variations in the effect of weather on tobacco consumption across the entire continental United States. The results allow health marketers to identify areas that will be most responsive to marketing efforts aimed at curtailing negative hedonic consumption and thus implement more effective, region-specific initiatives.