Korsgaardmahmood0029

The mechanistic studies revealed that the presence of retinoid X receptor alpha (RXRα) is essential to repress HNF4α activity in the presence of PPARα, and this interaction accelerates HNF4α degradation via the proteasome pathway. These results showed that PPARα can downregulate liver amino acid catabolism in the presence of RXRα by inhibiting HNF4α activity.Diverse snail species serve as intermediate hosts of the parasitic nematode Angiostrongylus cantonensis, the etiological agent of human neuroangiostrongyliasis. However, levels of A. cantonensis infection prevalence and intensity vary dramatically among these host species. Factors contributing to this variation are largely unknown. Environmental factors, such as precipitation and temperature, have been correlated with overall A. cantonensis infection levels in a locale, but the influence of environment on infection in individual snail species has not been addressed. We identified levels of A. cantonensis prevalence and intensity in 16 species of snails collected from 29 sites along an environmental gradient on the island of Oahu, Hawaii. The relationship between infection levels of individual species and their environment was evaluated using AIC model selection of Generalized Linear Mixed Models incorporating precipitation, temperature, and vegetation cover at each collection site. Our results indicate that dfectious larvae (infection intensity) in all infected snail species. This study highlights the variation of infection prevalence and intensity in individual gastropod species, the individualistic nature of interactions between host species and their environment, and the implications for human neuroangiostrongyliasis in different environments.

Memantine is a non-competitive antagonist of glutamatergic NMDA receptor that is mainly used in the treatment of Alzheimer's disease. The excitatory toxicity mediated by glutamate via glutamatergic receptor signals is considered to be one of the mechanisms mediating neuronal injury and cognitive impairment after exposure to a hypoxic environment at a high altitude. Therefore, in this study, we hypothesized that inhibiting glutamate signaling using memantine could alleviate neuronal injury and cognitive impairment in rats exposed to chronic hypoxia.

we made animal models in the natural environment of the Qinghai-Tibet Plateau at an altitude of 4300m, and used animal behavior, morphology, molecular biology and other methods to evaluate the impact of chronic hypoxia exposure on cognitive function and the neuroprotective effect of Memantine.

Our results showed that the expression of NMDA receptors increased, while the expression of AMPA receptors decreased, after 4weeks of chronic hypoxia exposure. Concomitantly, apoptotic neuronal cell death in the hippocampus and frontal cortex was significantly increased, along with levels of oxidative stress, whereas innate ability to inhibit free radicals decreased. Moreover, after 8weeks of hypoxia exposure, learning, memory, and space exploration abilities were significantly decreased. Notably, after treatment with memantine, apoptotic neuronal cell death, oxidative stress, and free radical levels decreased, and the cognitive function of the animals improved.

Present study shows that chronic hypoxia can produce the excitatory toxicity leading to neural injury and cognitive impairment that can be suppressed with memantine treatment by inhibiting excitatory toxicity.

Present study shows that chronic hypoxia can produce the excitatory toxicity leading to neural injury and cognitive impairment that can be suppressed with memantine treatment by inhibiting excitatory toxicity.Schizophrenia is a neurodevelopmental psychiatric disorder, encompassing genetic and environmental risk factors. For several decades, investigators have been implementing the use of lesions of the neonatal rodent hippocampus to model schizophrenia, resulting in a broad spectrum of adult schizophrenia-related behavioral changes. Despite the extensive use of these proposed animal models of schizophrenia, the mechanisms by which these lesions result in schizophrenia-like behavioral alterations remain unclear. Here we provide in vivo evidence that transient pharmacological inactivation of the hippocampus via tetrodotoxin microinjections or a genetic reduction in brain derived neurotrophic factor (BDNF) protein levels (BDNF+/- rats) lead to global DNA hypomethylation, disrupted maturation of the neuronal nucleus and aberrant acoustic startle response in the adult rat. The similarity between the effects of the two treatments strongly indicate that BDNF signaling is involved in effects obtained after the TTX microinjections. These findings may shed light on the cellular mechanisms underlying the phenotypical features of neonatal transient inhibition of the hippocampus as a preclinical model of schizophrenia and suggest that BDNF signaling represents a target pathway for development of novel treatment therapies.Levodopa-induced dyskinesia (LID) is experienced by most patients of Parkinson's disease (PD) upon the long-term use of the dopamine precursor levodopa. Striatal dopaminergic signaling plays a critical role in the pathogenesis of LID through its interactions with dopamine receptors. The specific roles of striatal dopaminergic D5 receptors in the pathophysiological process of LID are still poorly established. In the study, we investigated the role of striatal dopamine D5 receptor in LID by using PD rats with or without dyskinetic symptoms after chronic levodopa administration. The experimental results showed that the expression level of D5 receptors in the sensorimotor striatum of dyskinetic rats is significantly higher than that of the non-dyskinetic controls. The administration of levodopa increased c-Fos expression in a subpopulation of sensorimotor striatum neurons of dyskinetic rats, but not in non-dyskinetic rats. The majority of the c-Fos+ neurons activated by levodopa in the striatum are positive for D5 receptor staining. Intrastriatal injection of D1-like (D1 and D5) dopamine receptor antagonist, SCH-23390, significantly inhibited dyskinetic behavior in dyskinetic rats after the injection of levodopa, meanwhile, intrastriatal administration of SKF-83959, a partial D5 receptor agonist, yielded significant dyskinetic movements in dyskinetic rats without levodopa. In contrast, intrastriatal perfusion of small interfering RNA directed against DRD5 downregulated D5 receptors expression and moderately inhibited dyskinetic behavior of dyskinetic animals. A-769662 molecular weight Our data suggested that the striatal dopamine D5 receptor might play a novel role in the pathophysiology of LID.