Shoemakerbojesen2239

This study proves that the concrete concept should be visualized according to its appearance, not the most striking feature or function; but the visulization of abstract concept shows less difference after a concreteness transition.Rodent animals exposed to early maternal separation (EMS) show abnormal behaviors. Our previous study reported that autophagy is inhibited in the hippocampus of EMS rats, and hyperforin (HYP) alleviates depressive-like and anxious-like behaviors induced by EMS. However, the underlying mechanism of HYP is still unclear. In this study, we tested whether HYP alleviates the psychiatric disorders of EMS rats via activating autophagy. Pups were randomly divided into the control (CON) group, the EMS group, the EMS +3 mg/kg/day HYP (EMS + HYP) group and the EMS + treatment with 3 mg/kg/day fluoxetine (EMS + FT) group. Pups were separated from their mothers for 6 h every day from postnatal day 1 (PD1) to PD21 except pups of the CON group. Besides, HYP and FT were administered from PD22 to PD35 in the EMS + HYP group and the EMS + FT group respectively. Data showed that HYP not only reduced the level of glutamate, decreased the expression of N-methyl-d-aspartate receptor subunit 2B and postsynaptic density-95, but also increased the expression of synaptophysin of EMS rats. Interestingly, the expression of beclin-1 and the ratio of LC3II/LC3I were up-regulated in the EMS + HYP group. Moreover, HYP reduced the expression of the Notch1 receptor and the acetylation of H3K9 of EMS rats. In conclusion, our findings demonstrated that HYP ameliorates the depressive-like and anxious-like behaviors via activating autophagy in the hippocampus of EMS rats.Age-related pathologies like Alzheimer`s disease (AD) imply cellular responses directed towards repairing DNA damage. Postmitotic neurons show progressive accumulation of oxidized DNA during decades of brain aging, which is especially remarkable in AD brains. The characteristic cytoskeletal pathology of AD neurons is brought about by the progressive changes that neurons undergo throughout aging, and their irreversible nuclear transformation initiates the disease. This review focusses on critical molecular events leading to the loss of plasticity that underlies cognitive deficits in AD. During healthy neuronal aging, nuclear Tau participates in the regulation of the structure and function of the chromatin. The aberrant cell cycle reentry initiated for DNA repair triggers a cascade of events leading to the dysfunctional AD neuron, whereby Tau protein exits the nucleus leading to chromatin disorganization. Lamin A, which is not typically expressed in neurons, appears at the transformation from senile to AD neurons and contributes to halting the consequences of cell cycle reentry and nuclear Tau exit, allowing the survival of the neuron. Nevertheless, this irreversible nuclear transformation alters the nucleic acid and protein synthesis machinery as well as the nuclear lamina and cytoskeleton structures, leading to neurofibrillary tangles formation and final neurodegeneration.

The inflammatory response after traumatic brain injury (TBI) can contribute to secondary brain injury. RP101075, a sphingosine-1-phosphate receptor modulator, can attenuate various inflammatory responses. Here, we hypothesized that consecutive administration of RP101075 over 3 days could broadly suppress the TBI-induced inflammatory response and ameliorate the outcomes of TBI.

Young C57/BL6 mice were subjected to a controlled cortical impact (CCI) model. RP101075-treated mice exhibited significantly reduced scores on the modified neurological severity score (mNSS) test on days 3, 7, 14, and 21 after TBI, in comparison to TBI mice that received the vehicle. RP101075-treated mice had a remarkably decreased percentage of foot faults on the foot fault test on days 7, 14, and 21 after surgery, in comparison to TBI mice that received the vehicle. Using the wet brain weight/dry brain weight method, we found that RP101075 attenuated brain edema at 3 days post-TBI. According to the results of the Morris water mazenical setting.Exercise is recognized to increase the expression of neurotrophic genes in the hippocampus and prevent cognitive impairment. Histone deacetylase (HDAC) inhibitor acetylate histones and enhance gene transcription in epigenetic regulation. HDAC inhibitors are expected to be an efficacious pharmacological treatment for cognitive function. This study aimed to examine the effect of HDAC inhibitors and exercise on epigenetic markers and neurotrophic gene expression in the hippocampus to find a more enriched brain conditioning for cognitive function based on the synergic effects of pharmacological treatment and behavioral therapy. Thirteen-week-old male mice were divided into four groups. Triptolide Intraperitoneal administration of an HDAC inhibitor (1.2 g/kg sodium butyrate, NaB) and treadmill exercise (approximately 10 m/min for 60 min) were performed 5 days a week for 4 weeks. NaB administration increased the expression of an immediate-early gene, a neurotrophin, and a neurotrophin receptor in the hippocampus. These results indicate that HDAC inhibition could present an enriched platform for neuronal plasticity in the hippocampus and cognitive function. The novel object recognition test showed that NaB administration increased the score. Notably, the step-through passive avoidance test showed improved learning and memory in the presence of exercise and exercise, indicating that the mice acquired fear memory, specifically in the presence of NaB administration plus exercise. This study found that repetitive administration of HDAC inhibitors improved cognitive function and HDAC inhibitor administration plus exercise has a synergic effect on learning and memory, accompanying the enhancement of crucial gene transcriptions for neuronal plasticity in the hippocampus.Parkinson's disease (PD) is a neurodegenerative disorder linked with aging and primarily involves dopaminergic neuronal loss in the substantia nigra pars compacta (SNpc). The deregulation of genes associated with T2D has been demonstrated by proteomic research on Parkinson's symptoms patients. Various common pathways likely to link neurodegenerative mechanisms of PD include abnormal mitochondrial function, inflammation, apoptosis/autophagy and insulin signalling/glucose metabolism in T2DM. Several pathway components including phosphatidylinositol 3 kinase/protein kinase B (PI3K/Akt), glycogen synthase kinase-3 beta (GSK-3β) and nuclear factor kappa B (NF-κB) impairment is observed in PD. Numerous novel targets are being pursued in preclinical and clinical trials that target metabolic dysfunction in PD; that elevate insulin signaling pathways in dopaminergic neurons, and show improvement in motor and cognitive measures and produce significant neuroprotective effects in PD patients.