In this review, we explored how these metals affect brain physiology and their roles in the accumulation of toxic proteins (α-synuclein and Lewy bodies). We have also discussed the metals associated with neurotoxic effects and their prevention as management of PD. Our goal is to increase the awareness of metals as players in the onset and progression of PD.Autophagy is a highly conserved degradative process that has been associated with a number of neurological diseases. Autophagy-related protein 5 (ATG5) is one of the key genes for the regulation of the autophagy pathway. In this study, we investigated the potential relationship between ATG5 gene polymorphisms and epilepsy in Han Chinese population. We enrolled 112 patients with epilepsy and 100 healthy controls and detected the genotypic and allelic data of 6 single nucleotide polymorphisms (SNPs) in ATG5 (rs2245214, rs510432, rs548234, rs573775, rs6568431 and rs6937876). The associations of 6 SNPs and epilepsy were evaluated. The results revealed the genotypes of overdominant of rs510432 between controls and patients showed significant differences (Poverdominant = 0.003). Subgroup analysis showed a highly significant association of rs510432 with late-onset epilepsy (Poverdominant = 0.006), and rs548234 were associated with the susceptibility to temporal lobe epilepsy (Pcodominant = 0.002, Poverdominant = 0.006). Furthermore, ATG5 was not linked to either early-onset epilepsy or drug-resistant epilepsy (p > 0.0083). These results demonstrated an association of an ATG5 gene variant with epilepsy, and stronger associations with several subgroups of epilepsy were identified. Our study may provide novel evidence for the role of ATG5 in epilepsy, and contribute to our understanding of the molecular mechanisms of this chronic neurological disease.The voluntary movement demands integration between cognitive and motor functions. During the initial stages of motor learning until mastery of a new motor task, and during a demanding task that is not automatic, cognitive and motor functions can be perceived as independent from each other. Areas used for actually performing motor tasks are essentially the same used by Motor Imagery (MI). The main objective of this study was to investigate inhibition effects on cognitive functions of motor skills induced by low-frequency (1 Hz) Repetitive Transcranial Magnetic Stimulation (rTMS) at the sensory-motor integration site (Cz). In particular, the goal was to examine absolute alpha and beta power changes on frontal regions during Execution, Action observation, and Motor Imagery of finger movement tasks. Eleven healthy, right-handed volunteers of both sexes (5 males, 6 females; mean age 28 ± 5 years), with no history of psychiatric or neurological disorders, participated in the experiment. The execution task consisted of the subject flexing and extending the index finger. The action observation task involved watching a video of the same movement. The motor imagery task was imagining the flexion and extension of the index finger movement. After performing the tasks randomly, subjects were submitted to 15 min of low-frequency rTMS and performed the tasks again. All tasks were executed simultaneously with EEG signals recording. Our results demonstrated a significant interaction between rTMS and the three tasks in almost all analyzed regions showing that rTMS can affect the frontal region regarding Execution, Action observation, and Motor Imagery tasks.The brain is one of the most important and intricate organs in our bodies. Interpreting brain function and illustrating the changes and molecular mechanisms during physiological or pathological processes are essential but sometimes difficult to achieve. In addition to histology, ethology and pharmacology, the development of transcriptomics alleviates this condition by enabling high-throughput observation of the brain at various levels of anatomical specificity. Moreover, because human brain samples are scarce, the brains of nonhuman primates are important alternative models. Here in this review, we summarize the applications of transcriptomics in nonhuman primate brain studies, including investigations of brain development, aging, toxic effects and diseases. Overall, as a powerful tool with developmental potential, transcriptomics has been widely utilized in neuroscience.Cerebrovascular diseases endanger human health, and the physiological and pathological processes of cerebral ischemia/reperfusion injury (CIRI) are critical for the occurrence of these diseases and as targets for their treatment. Here, we evaluated the effects of harpagide-mediated pharmacological and genetic inhibition of sarco-endoplasmic reticulum Ca2+-ATPase (SERCA) in vitro in PC12 cells. The molecular mechanism by which harpagide protects PC12 cells against oxygen-glucose deprivation/reoxygenation (OGD/R) injury was investigated by evaluating the cell survival rate with the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay, assessing apoptosis by flow cytometry, determining the intracellular Ca2+ concentration ([Ca2+]i) by laser scanning confocal microscopy (LSCM), and measuring the expression of proteins related to SERCA and endoplasmic reticulum stress (ERS) by Western blotting. Lifirafenib solubility dmso The results revealed that harpagide significantly decreased thapsigargin (TG)-induced apoptosis of PC12 cells, downregulated the expression of ERS-related markers, considerably improved the TG-induced expression of SERCA-related proteins and reduced the [Ca2+]i, suggesting that harpagide effectively inhibited ERS directly. Moreover, harpagide did not significantly reduce OGD/R-induced apoptosis but increased the expression of ERS markers in PC12/SERCA- cells, indicating that harpagide targets SERCA to protect against CIRI by suppressing ERS-mediated apoptosis.Parkinson disease (PD) is a progressive movement functionality disorder resulting in tremor and inability to execute voluntary functions combined with the preponderant non-motor disturbances encompassing constipation and gastrointestinal irritation. Despite continued research, the pathogenesis of PD is not yet clear. The available class of drugs for effective symptomatic management of PD includes a combination of levodopa and carbidopa. In recent past, the link between gut with PD has been explored. According to recent preclinical evidence, pathogens such as virus or bacterium may initiate entry into the gut via the nasal cavity that may aggravate lewy pathology in the gut that eventually propagates and progresses towards the brain via the vagus nerve resulting in the prodromal non-motor symptoms. Additionally, experimental evidence also suggests that alpha-synuclein misfolding commences at a very early stage in the gut and is transported via the vagus nerve prior to seeding PD pathology in the brain. However, this progression and resultant deterioration of the neurones can effectively be altered by an autophagy inducer, Trehalose, although the mechanism behind it is still enigmatic. Hence, this review will mainly focus on analysing the basic components of the gut that might be responsible for aggravating lewy pathology, the mediator(s) responsible for transmission of PD pathology from gut to brain and the important role of trehalose in ameliorating gut dysbiosis related PD complications that would eventually pave the way for therapeutic management of PD.This research aimed to examine the nutritious supplementary function of 18β-Glycyrrhetinic acid (18β-GA) in moderating the myelin sheath destruction and behavioral impairments observed in the cuprizone model of demyelination. Mice were fed daily on food containing cuprizone (0.3 %) and given doses of 18β-GA (5 or 1 mg/kg) for a period of five weeks. The groups treated with 18β-GA exhibited improvements in exploratory behavior, locomotive activity, and weight. As assessed using luxol-fast blue and myelin basic protein (MBP) staining, which were used to detect demyelination in the brain, 18β-GA both reduced and prevented instances of cuprizone-induced demyelinating lesions; treatment with 18β-GA also caused the MBP level in the corpus callosum to increase. Furthermore, alongside these positive results following 18β-GA treatment, microglial polarisation was also observed to shift towards the beneficial M2 phenotype. The results of this research thus indicate the potential clinical application of 18β-GA for the prevention of myelin damage and behavioral dysfunction.Small Rho GTPases such as Cdc42 and Rac1 regulate peripheral myelination during development. Deletion of Rac1 in Schwann cell conditional knockout mice causes a delay in the process of radial sorting, followed by hypomyelination as well as defective PAK1 activation and high number of immature Oct6+ Schwann cells. Rac3 has been shown to have redundant, specific and even opposite functions to Rac1 depending on the cell type, age and other factors. In neuronal cells, evidence suggests that Rac3 may oppose Rac1 by disrupting PAK1-GIT1-Paxillin signaling thus preventing cell differentiation and extension of lamellipodia. Therefore, we tested if these Rho GTPases have similar or opposite functions in Schwann cells, by deleting the genes for both proteins in mice during peripheral myelination. At P30, global deletion of Rac3 alleviates the developmental defects on axonal sorting and hypomyelination that are caused by Schwann cell conditional ablation of Rac1. Moreover, Rac3 deletion also reverses the arrest of Schwann cells at the Oct6+ stage and ameliorates the defects in PAK1 phosphorylation observed in Rac1 deficient mice. This partial rescue of the phenotype declines later on with aging. Since double transgenic animals showed dysmyelination without axonal degeneration at P60, we postulate that this deterioration is not likely due to loss of Rac3 in neurons, but it seems to be a Schwann cell-specific defect in the maintenance of myelin.Transcranial static magnetic field stimulation (tSMS) has inhibitory neuromodulatory effects on the human brain. Most of the studies on static magnetic fields have been performed in vitro. To further understand the biological mechanisms of tSMS, we investigated the effects of in vivo tSMS on motor behavior in normal awake rats. The skull of a male Wistar rat was exposed and a polyethylene tube was attached to the skull using dental cement at the center of the motor cortex (n = 7) or the other cortex (n = 6). By attaching a cylindrical NdFeB neodymium magnet into the tube, in vivo tSMS (REAL) was performed. For SHAM, we applied a similar size non-magnetic stainless-steel cylinder. All rats received twice each SHAM and REAL stimulation every two days using a crossover design, and motor function was measured during the stimulation. Activity level and asymmetry of forelimb use were not affected, but less accurate movements in the horizontal ladder test were found in REAL stimulation of the motor cortex. This study shows that in vivo tSMS has inhibitory neuromodulatory effects on motor behavior depending on the stimulated region on the rat cortex.

The aim of the present study was to examine the effects of different quercetin pretreatment doses on focal epileptiform activity induced by penicillin in adult male rat cortex.

Twenty-eight male Wistar rats weighing 200-235 g were randomly divided into four groups control (only penicillin-injected group) and penicillin + 25, 50 or 100 mg/kg quercetin doses. All quercetin-treated rats had a daily single dose of 25, 50 or 100 mg/kg intraperitoneally administered quercetin for 21 days, and the last dose was given 30 min before the penicillin injection. Epileptiform activity was induced by a single intracortical (i.c.) microinjection of penicillin (500 units/2.5 μl) into left motor cortex. After penicillin injection ECoG was recorded for the following 180 min.

Quercetin pretreatments of 25, 50 and 100 mg/kg significantly increased the duration of latency (initial spike activity) and decreased spike frequency of the epileptiform activity compared to the control group (p < 0.05). Duration of latency was significantly longer in 25 mg/kg quercetin pretreatment group compared to 100 mg/kg group (p < 0.