Songbates7807

Parkinson's disease (PD) is a neurodegenerative disorder, and the hallmarks of this disease include iron deposition and α-synuclein (α-syn) aggregation. RMC-6236 supplier Hepcidin could reduce iron in the central and peripheral nervous systems. Here, we hypothesized that hepcidin could further decrease α-syn accumulation via reducing iron. Therefore, rotenone or α-syn was introduced into human neuroblastoma SH-SY5Y cells to imitate the pathological progress of PD in vitro. This study investigated the clearance effects of hepcidin on α-syn induced by a relatively low concentration of rotenone exposure or α-syn overexpression to elucidate the potential clearance pathway involved in this process. We demonstrated that SH-SY5Y cell viability was impaired after rotenone treatment in a dose-dependent manner. α-syn expression and iron content increased under a low concentration rotenone (25 nM for 3 days) treatment in SH-SY5Y cells. Pre-treatment with hepcidin peptide suppressed the abovementioned effects of rotenone. However, hepcidin did not affect treatment with rotenone under high iron conditions. Hepcidin also played a role in reducing α-syn accumulation in rotenone and α-syn overexpression conditions. We identified that the probable clearance effect of hepcidin on α-syn was mediated by the autophagy pathway using pretreatment with autophagy inhibitors (3-MA and CQ) and detection of autophagy protein markers (LC3II/I and p62). In conclusion, hepcidin eliminated α-syn expression via the autophagy pathway in rotenone-treated and α-syn overexpression SH-SY5Y cells. This study highlights that hepcidin may offer a potential therapeutic perspective in α-syn accumulation diseases.Rhythmic limb movements during locomotion are controlled by central pattern generator (CPG) circuits located in the spinal cord. It is considered that these circuits are composed of individual rhythm generators (RGs) for each limb interacting with each other through multiple commissural and long propriospinal circuits. The organization and operation of each RG are not fully understood, and different competing theories exist about interactions between its flexor and extensor components, as well as about left-right commissural interactions between the RGs. The central idea of circuit organization proposed in this study is that with an increase of excitatory input to each RG (or an increase in locomotor speed) the rhythmogenic mechanism of the RGs changes from "flexor-driven" rhythmicity to a "classical half-center" mechanism. We test this hypothesis using our experimental data on changes in duration of stance and swing phases in the intact and spinal cats walking on the ground or tied-belt treadmills (symmetric conditions) or split-belt treadmills with different left and right belt speeds (asymmetric conditions). We compare these experimental data with the results of mathematical modeling, in which simulated CPG circuits operate in similar symmetric and asymmetric conditions with matching or differing control drives to the left and right RGs. The obtained results support the proposed concept of state-dependent changes in RG operation and specific commissural interactions between the RGs. The performed simulations and mathematical analysis of model operation under different conditions provide new insights into CPG network organization and limb coordination during locomotion.Humulus lupulus L. (hops) is a major constituent of beer. It exhibits neuroactive properties that make it useful as a sleeping aid. These effects are hypothesized to be mediated by an increase in GABAA receptor function. In the quest to uncover the constituents responsible for the sedative and hypnotic properties of hops, recent evidence revealed that humulone, a prenylated phloroglucinol derivative comprising 35-70% of hops alpha acids, may act as a positive modulator of GABAA receptors at low micromolar concentrations. This raises the question whether humulone plays a key role in hops pharmacological activity and potentially interacts with other modulators such as ethanol, bringing further enhancement in GABAA receptor-mediated effects of beer. Here we assessed electrophysiologically the positive modulatory activity of humulone on recombinant GABAA receptors expressed in HEK293 cells. We then examined humulone interactions with other active hops compounds and ethanol on GABA-induced displacement of [3H]EBOBuced sleep onset, sleep duration was increased dose-dependently down to 10 mg/kg (i.p.). Our findings confirmed humulone's positive allosteric modulation of GABAA receptor function and displayed its sedative and hypnotic behavior. Humulone modulation can be potentially enhanced by ethanol and hops modulators suggesting a probable enhancement in the intoxicating effects of ethanol in hops-enriched beer.Microstructure imaging by means of multidimensional diffusion encoding is increasingly applied in clinical research, with expectations that it yields a parameter that better correlates with clinical disability than current methods based on single diffusion encoding. Under the assumption that diffusion within a voxel can be well described by a collection of diffusion tensors, several parameters of this diffusion tensor distribution can be derived, including mean size, variance of sizes, orientational dispersion, and microscopic anisotropy. The information provided by multidimensional diffusion encoding also enables us to decompose the sources of the conventional fractional anisotropy and mean kurtosis. In this study, we explored the utility of the diffusion tensor distribution approach for characterizing white-matter degeneration in aging and in Parkinson disease by using double diffusion encoding. Data from 23 healthy older subjects and 27 patients with Parkinson disease were analyzed. Advanced age was associated with greater mean size and size variances, as well as smaller microscopic anisotropy. By analyzing the parameters underlying diffusion kurtosis, we found that the reductions of kurtosis in aging and Parkinson disease reported in the literature are likely driven by the reduction in microscopic anisotropy. Furthermore, microscopic anisotropy correlated with the severity of motor impairment in the patients with Parkinson disease. The present results support the use of multidimensional diffusion encoding in clinical studies and are encouraging for its future clinical implementation.Cerebral ischemia induces neuronal cell death and causes various kinds of brain dysfunction. Therefore, prevention of neuronal cell death is most essential for protection of the brain. On the other hand, it has been reported that epigenetics including DNA methylation plays a pivotal role in pathogenesis of some diseases such as cancer. Accumulating evidences indicate that aberrant DNA methylation is related to cell death. However, DNA methylation after cerebral ischemia has not been fully understood yet. The aim of this present study was to investigate the relationships between DNA methylation and neuronal cell death after cerebral ischemia. We examined DNA methylation under the ischemic condition by using transient middle cerebral artery occlusion and reperfusion (MCAO/R) model rats and N-methyl-D-aspartate (NMDA)-treated cortical neurons in primary culture. In this study, we demonstrated that DNA methylation increased in these neurons 24 h after MCAO/R and that DNA methylation, possibly through activation of DNA methyltransferases (DNMT) 3a, increased in such neurons immediately after NMDA treatment. Furthermore, NMDA-treated neurons were protected by treatment with a DNMT inhibitor that were accompanied by inhibition of DNA methylation. Our results showed that DNA methylation would be an initiation factor of neuronal cell death and that inhibition of such methylation could become an effective therapeutic strategy for stroke.The influence of non-visual information on visual awareness judgments has recently gained substantial interest. Using single-pulse transcranial magnetic stimulation (TMS), we investigate the potential contribution of evidence from the motor system to judgment of visual awareness. We hypothesized that TMS-induced activity in the primary motor cortex (M1) would increase reported visual awareness as compared to the control condition. Additionally, we investigated whether TMS-induced motor-evoked potential (MEP) could measure accumulated evidence for stimulus perception. Following stimulus presentation and TMS, participants first rated their visual awareness verbally using the Perceptual Awareness Scale (PAS), after which they responded manually to a Gabor orientation identification task. Delivering TMS to M1 resulted in higher average awareness ratings as compared to the control condition, in both correct and incorrect identification task response trials, when the hand with which participants responded was contralateral to the stimulated hemisphere (TMS-response-congruent trials). This effect was accompanied by longer PAS response times (RTs), irrespective of the congruence between TMS and identification response. Moreover, longer identification RTs were observed in TMS-response-congruent trials in the M1 condition as compared to the control condition. Additionally, the amplitudes of MEPs were related to the awareness ratings when response congruence was taken into account. We argue that MEP can serve as an indirect measure of evidence accumulated for stimulus perception and that longer PAS RTs and higher amplitudes of MEPs in the M1 condition reflect integration of additional evidence with visual awareness judgment. In conclusion, we advocate that motor activity influences perceptual awareness judgments.

Subjective cognitive decline (SCD) and amnestic mild cognitive impairment (aMCI) were considered to be a continuum of Alzheimer's disease (AD) spectrum. The abnormal topological architecture and rich-club organization in the brain functional network can reveal the pathology of the AD spectrum. However, few studies have explored the disrupted patterns of diverse club organizations and the combination of rich- and diverse-club organizations in SCD and aMCI.

We collected resting-state functional magnetic resonance imaging data of 19 SCDs, 29 aMCIs, and 28 healthy controls (HCs) from the Alzheimer's Disease Neuroimaging Initiative. Graph theory analysis was used to analyze the network metrics and rich- and diverse-club organizations simultaneously.

Compared with HC, the aMCI group showed altered small-world and network efficiency, whereas the SCD group remained relatively stable. The aMCI group showed reduced rich-club connectivity compared with the HC. In addition, the aMCI group showed significantly increight be potential biomarkers in the diagnosis of the AD spectrum.When viewed cross-sectionally, aging seems to negatively affect speech comprehension. However, aging is a heterogeneous process, and variability among older adults is typically large. In this study, we investigated language comprehension as a function of individual differences in older adults. Specifically, we tested whether hearing thresholds, working memory, inhibition, and individual alpha frequency would predict event-related potential amplitudes in response to classic psycholinguistic manipulations at the sentence level. Twenty-nine healthy older adults (age range 61-76 years) listened to English sentences containing reduced relative clauses and object-relative clauses while their electroencephalogram was recorded. We found that hearing thresholds and working memory predicted P600 amplitudes early during reduced relative clause processing, while individual alpha frequency predicted P600 amplitudes at a later point in time. The results suggest that participants with better hearing and larger working memory capacity simultaneously activated both the preferred and the dispreferred interpretation of reduced relative clauses, while participants with worse hearing and smaller working memory capacity only activated the preferred interpretation.