Low p-SYN1 (Ser-553) Expression Leads to Abnormal Neurotransmitter Release of GABA Induced by Up-Regulated Cdk5 after Microwave Exposure: Insights on Protection and Treatment of Microwave-Induced Cognitive Dysfunction

With the wide application of microwave technology, concerns about its health impact have arisen. The signal transmission mode of the central nervous system and neurons make it particularly sensitive to electromagnetic exposure. It has been reported that abnormal release of amino acid neurotransmitters is mediated by alteration of p-SYN1 after microwave exposure, which results in cognitive dysfunction. As the phosphorylation of SYN1 is regulated by different kinases, in this study we explored the regulatory mechanisms of SYN1 fluctuations following microwave exposure and its subsequent effect on GABA release, aiming to provide clues on the mechanism of cognitive impairment caused by microwave exposure. In vivo studies with Timm and H&E staining were adopted and the results showed abnormality in synapse formation and neuronal structure, explaining the previously-described deficiency in cognitive ability caused by microwave exposure. The observed alterations in SYN1 level, combined with the results of earlier studies, indicate that SYN1 and its phosphorylation status (ser-553 and ser62/67) may play a role in the abnormal release of neurotransmitters. Thus, the role of Cdk5, the upstream kinase regulating the formation of p-SYN1 (ser-553), as well as that of MEK, the regulator of p-SYN1 (ser-62/67), were investigated both in vivo and in vitro. The results showed that Cdk5 was a negative regulator of p-SYN1 (ser-553) and that its up-regulation caused a decrease in GABA release by reducing p-SYN1 (ser-553). While further exploration still needed to elaborate the role of p-SYN1 (ser-62/67) for neurotransmitter release, MEK inhibition had was no impact on p-Erk or p-SYN1 (ser-62/67) after microwave exposure. In conclusion, the decrease of p-SYN1 (ser-553) may result in abnormalities in vesicular anchoring and GABA release, which is caused by increased Cdk5 regulated through Calpain-p25 pathway after 30 mW/cm2 microwave exposure. This study provided a potential new strategy for the prevention and treatment of microwave-induced cognitive dysfunction.

Diamond Concept as Principle for the Development of Spinal Cord Scaffold: A Literature Review

INTRODUCTION: Spinal cord injury (SCI) has been bringing detrimental impacts on the affected individuals. However, not only that, it also brings a tremendous effect on the socioeconomic and health-care system. Treatment regimen and strategy for SCI patient have been under further research. DISCUSSION: The main obstacles of regeneration on neuronal structure are the neuroinflammatory process and poor debris clearance, causing a longer healing process and an extensive inflammation process due to this particular inflammatory process. To resolve all of the mentioned significant issues in SCIs neuronal regeneration, a comprehensive model is necessary to analyze each step of progressive condition in SCI. In this review, we would like to redefine a comprehensive concept of the “Diamond Concept” from previously used in fracture management to SCI management, which consists of cellular platform, cellular inductivity, cellular conductivity, and material integrity. The scaffolding treatment strategy for SCI has been widely proposed due to its flexibility. It enables the physician to combine another treatment method such as neuroprotective or neuroregenerative or both in one intervention. CONCLUSION: Diamond concept perspective in the implementation of scaffolding could be advantageous to increase the outcome of SCI treatment.

A Study of Anxiety on Experimental Epileptic Rat Models using Dark Light Box

The word neurodegeneration refers to defects in neuronal structure and consequently its function. The main characteristics of these disorders are relentless progression and cognitive declination. Epilepsy is one of the neurodegenerative disorders, around 50 million people in the world are affected with. Though it is one of the major health problems in the present society, there are several gaps in understanding the consequences related to neurological disorders. As research works related to neurodegeneration is very much limited in India we have planned one as an initiative. We segregated 8 animal groups, each with 6 animals for this work. The animal groups are LC, CO, AC15, AC25, AC35, BA10, BA15 and BA20. This study was conducted on 10th day after the lesion by considering the day of lesion as day ‘1’ and the next day as day 2nd. All the animals were recovered completely within these 10 days and were put in the dark light box to analyse the anxiety level of the animals, so as to analyse the effect of the drug employed. This particular study clearly supported the efficacy of the drug as the drug group animals were less anxious or even behaved normal. Both the crude extract and the selected active principle have proved their efficacy by the study.

EZH2 inhibition in glioblastoma stem cells increases the expression of neuronal genes and the neuronal developmental regulators ZIC2, ZNF423 and MAFB

Glioblastoma multiforme (GBM) is an aggressive brain cancer with a very poor prognosis. It has been shown that GBM stem cells within a GBM tumour have increased resistance to standard therapies, so new approaches are needed to increase the range of treatment options available. Here we use two GBM stem cell lines, representing the classical/pro-neural and mesenchymal GBM subtypes, to investigate the effects of three different EZH2 inhibitors on GBM stem cell survival and gene expression: EPZ6438, GSK343 and UNC1999. EZH2 is the catalytic component of the PRC2 chromatin repressor complex, which represses transcription through methylation of histone H3 at lysine 27. Both cell lines showed significantly reduced colony formation after 48-hour exposure to the inhibitors, indicating they were sensitive to all three EZH2 inhibitors. RNA-seq analysis revealed that all three EZH2 inhibitors led to increased expression of genes related to neurogenesis and/or neuronal structure in both GBM stem cell lines. Chromatin immunoprecipitation (ChIP-Seq) was used to identify potential direct targets of the histone methylation activity of EZH2 that might be driving the increase in neuronal gene expression. Three genes were identified as candidate regulatory targets common to both cell lines: MAFB, ZIC2 and ZNF423. These transcription factors all have known roles in regulating neurogenesis, brain development and/or neuronal function. Through analysis of three different EZH2 inhibitors and two GBM stem cell lines, this study demonstrates a common underlying mechanism for how inhibition of EZH2 activity reduces GBM stem cell proliferation and survival.

The Use of Ginkgo Biloba L. as a Neuroprotective Agent in the Alzheimer’s Disease

Alzheimer’s disease, a neurodegenerative disease, is one of the most common causes of dementia if elderly people worldwide. Alzheimer’s disease leads to the alienation of individuals and their exclusion from social and professional life. It is characterized mainly by the degradation of memory and disorientation, which occurs as a result of the loss of neuronal structure and function in different brain areas. In recent years, more and more attention has been paid to use in the treatment of natural bioactive compounds that will be effective in neurodegenerative diseases, including Alzheimer’s disease. G. biloba L. and its most frequently used standardized extract (EGb 761), have been used for many years in supportive therapy and in the prevention of cognitive disorders. The paper presents an overview of reports on the pathogenesis of Alzheimer’s disease, as well as a summary of the properties of G. biloba extract and its effects on the possible pathogenesis of the disease. By exploring more about the pathogenesis of the disease and the benefits of G. biloba extract for patients with Alzheimer’s disease, it will be possible to create an individualized therapeutic protocol to optimize the treatment.

Truncating tau reveals different pathophysiological actions of oligomers in single neurons

Tau protein is involved in maintaining neuronal structure. In Alzheimer’s disease, small numbers of tau molecules can aggregate to form oligomers. However, how these oligomers produce changes in neuronal function remains unclear. Previously, oligomers made from full-length human tau were found to have multiple effects on neuronal properties. Here we have cut the tau molecule into two parts: the first 123 amino acids and the remaining 124-441 amino acids. These truncated tau molecules had specific effects on neuronal properties, allowing us to assign the actions of full-length tau to different regions of the molecule. We identified one key target for the effects of tau, the voltage gated sodium channel, which could account for the effects of tau on the action potential. By truncating the tau molecule, we have probed the mechanisms that underlie tau dysfunction, and this increased understanding of tau’s pathological actions will build towards developing future tau-targeting therapies.

Foreground Estimation in Neuronal Images With a Sparse-Smooth Model for Robust Quantification

3D volume imaging has been regarded as a basic tool to explore the organization and function of the neuronal system. Foreground estimation from neuronal image is essential in the quantification and analysis of neuronal image such as soma counting, neurite tracing and neuron reconstruction. However, the complexity of neuronal structure itself and differences in the imaging procedure, including different optical systems and biological labeling methods, result in various and complex neuronal images, which greatly challenge foreground estimation from neuronal image. In this study, we propose a robust sparse-smooth model (RSSM) to separate the foreground and the background of neuronal image. The model combines the different smoothness levels of the foreground and the background, and the sparsity of the foreground. These prior constraints together contribute to the robustness of foreground estimation from a variety of neuronal images. We demonstrate the proposed RSSM method could promote some best available tools to trace neurites or locate somas from neuronal images with their default parameters, and the quantified results are similar or superior to the results that generated from the original images. The proposed method is proved to be robust in the foreground estimation from different neuronal images, and helps to improve the usability of current quantitative tools on various neuronal images with several applications.

Optimization of Neurite Tracing and Further Characterization of Human Monocyte-Derived-Neuronal-like Cells

Deficits in neuronal structure are consistently associated with neurodevelopmental illnesses such as autism and schizophrenia. Nonetheless, the inability to access neurons from clinical patients has limited the study of early neurostructural changes directly in patients’ cells. This obstacle has been circumvented by differentiating stem cells into neurons, although the most used methodologies are time consuming. Therefore, we recently developed a relatively rapid (~20 days) protocol for transdifferentiating human circulating monocytes into neuronal-like cells. These monocyte-derived-neuronal-like cells (MDNCs) express several genes and proteins considered neuronal markers, such as MAP-2 and PSD-95. In addition, these cells conduct electrical activity. We have also previously shown that the structure of MDNCs is comparable with that of human developing neurons (HDNs) after 5 days in culture. Moreover, the neurostructure of MDNCs responds similarly to that of HDNs when exposed to colchicine and dopamine. In this manuscript, we expanded our characterization of MDNCs to include the expression of 12 neuronal genes, including tau. Following, we compared three different tracing approaches (two semi-automated and one automated) that enable tracing using photographs of live cells. This comparison is imperative for determining which neurite tracing method is more efficient in extracting neurostructural data from MDNCs and thus allowing researchers to take advantage of the faster yield provided by these neuronal-like cells. Surprisingly, it was one of the semi-automated methods that was the fastest, consisting of tracing only the longest primary and the longest secondary neurite. This tracing technique also detected more structural deficits. The only automated method tested, Volocity, detected MDNCs but failed to trace the entire neuritic length. Other advantages and disadvantages of the three tracing approaches are also presented and discussed.