Extracellular Vesicles in CNS Developmental Disorders

The central nervous system (CNS) is the most complex structure in the body, consisting of multiple cell types with distinct morphology and function. Development of the neuronal circuit and its function rely on a continuous crosstalk between neurons and non-neural cells. It has been widely accepted that extracellular vesicles (EVs), mainly exosomes, are effective entities responsible for intercellular CNS communication. They contain membrane and cytoplasmic proteins, lipids, non-coding RNAs, microRNAs and mRNAs. Their cargo modulates gene and protein expression in recipient cells. Several lines of evidence indicate that EVs play a role in modifying signal transduction with subsequent physiological changes in neurogenesis, gliogenesis, synaptogenesis and network circuit formation and activity, as well as synaptic pruning and myelination. Several studies demonstrate that neural and non-neural EVs play an important role in physiological and pathological neurodevelopment. The present review discusses the role of EVs in various neurodevelopmental disorders and the prospects of using EVs as disease biomarkers and therapeutics.     

Behavioral depression during cocaine withdrawal is associated with decreased spontaneous activity of ventral tegmental area dopamine neurons.

Withdrawal from an escalating-dose, bingelike regimen of cocaine administration in rats produced significantly depressed levels of locomotor activity during the nocturnal portion of the day-night cycle. This effect was observed during the first 48 hrs of testing. Extracellular single-unit recordings of ventral tegmental area (VTA) dopamine (DA) neurons revealed no differences between saline- and cocaine-treated rats with respect to basal firing rates. However, significantly fewer spontaneously active VTA DA neurons were encountered in rats withdrawn from binge cocaine. As with the nocturnal hypoactivity, this effect was observed only during the first 48 hrs of withdrawal. These findings suggest that short-term DA neuron dysfunction during cocaine withdrawal temporally corresponds to behavioral disruptions that are similar to those described in human addicts. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Methamphetamine Blocks Adenosine A2A Receptor Activation via Sigma 1 and Cannabinoid CB1 Receptors

Methamphetamine is, worldwide, one of the most consumed drugs of abuse. One important side effect is neurodegeneration leading to a decrease in life expectancy. The aim of this paper was to check whether the drug affects one of the receptors involved in neurodegeneration/neuroprotection events, namely the adenosine A_2A receptor (A_2AR). First, we noticed that methamphetamine does not affect A_2A functionality if the receptor is expressed in a heterologous system. However, A_2AR becomes sensitive to the drug upon complexes formation with the cannabinoid CB₁ receptor (CB₁R) and the sigma 1 receptor (σ₁R). Signaling via both adenosine A_2AR and cannabinoid CB₁R was affected by methamphetamine in cells co-expressing the two receptors. In striatal primary cultures, the A_2AR–CB₁R heteromer complex was detected and methamphetamine not only altered its expression but completely blocked the A_2AR- and the CB₁R-mediated activation of the mitogen activated protein kinase (MAPK) pathway. In conclusion, methamphetamine, with the participation of σ₁R, alters the expression and function of two interacting receptors, A_2AR, which is a therapeutic target for neuroprotection, and CB₁R, which is the most abundant G protein-coupled receptor (GPCR) in the brain.     

Utilizing an Animal Model to Identify Brain Neurodegeneration-Related Biomarkers in Aging

Glycine N-methyltransferase (GNMT) regulates S-adenosylmethionine (SAMe), a methyl donor in methylation. Over-expressed SAMe may cause neurogenic capacity reduction and memory impairment. GNMT knockout mice (GNMT-KO) was applied as an experimental model to evaluate its effect on neurons. In this study, proteins from brain tissues were studied using proteomic approaches, Haemotoxylin and Eosin staining, immunohistochemistry, Western blotting, and ingenuity pathway analysis. The expression of Receptor-interacting protein 1(RIPK1) and Caspase 3 were up-regulated and activity-dependent neuroprotective protein (ADNP) was down-regulated in GNMT-KO mice regardless of the age. Besides, proteins related to neuropathology, such as excitatory amino acid transporter 2, calcium/calmodulin-dependent protein kinase type II subunit alpha, and Cu-Zn superoxide dismutase were found only in the group of aged wild-type mice; 4-aminobutyrate amino transferase, limbic system-associated membrane protein, sodium- and chloride-dependent GABA transporter 3 and ProSAAS were found only in the group of young GNMT-KO mice and are related to function of neurons; serum albumin and Rho GDP dissociation inhibitor 1 were found only in the group of aged GNMT-KO mice and are connected to neurodegenerative disorders. With proteomic analyses, a pathway involving Gonadotropin-releasing hormone (GnRH) signal was found to be associated with aging. The GnRH pathway could provide additional information on the mechanism of aging and non-aging related neurodegeneration, and these protein markers may be served in developing future therapeutic treatments to ameliorate aging and prevent diseases.     

Functional and Molecular Properties of DYT-SGCE Myoclonus-Dystonia Patient-Derived Striatal Medium Spiny Neurons

Myoclonus-dystonia (DYT-SGCE, formerly DYT11) is characterized by alcohol-sensitive, myoclonic-like appearance of fast dystonic movements. It is caused by mutations in the SGCE gene encoding ε-sarcoglycan leading to a dysfunction of this transmembrane protein, alterations in the cerebello-thalamic pathway and impaired striatal plasticity. To elucidate underlying pathogenic mechanisms, we investigated induced pluripotent stem cell (iPSC)-derived striatal medium spiny neurons (MSNs) from two myoclonus-dystonia patients carrying a heterozygous mutation in the SGCE gene (c.298T>G and c.304C>T with protein changes W100G and R102X) in comparison to two matched healthy control lines. Calcium imaging showed significantly elevated basal intracellular Ca²⁺ content and lower frequency of spontaneous Ca²⁺ signals in SGCE MSNs. Blocking of voltage-gated Ca²⁺ channels by verapamil was less efficient in suppressing KCl-induced Ca²⁺ peaks of SGCE MSNs. Ca²⁺ amplitudes upon glycine and acetylcholine applications were increased in SGCE MSNs, but not after GABA or glutamate applications. Expression of voltage-gated Ca²⁺ channels and most ionotropic receptor subunits was not altered. SGCE MSNs showed significantly reduced GABAergic synaptic density. Whole-cell patch-clamp recordings displayed elevated amplitudes of miniature postsynaptic currents and action potentials in SGCE MSNs. Our data contribute to a better understanding of the pathophysiology and the development of novel therapeutic strategies for myoclonus-dystonia.     

航空有源滤波器自适应谐波检测仿真研究

介绍了基于自适应滤波理论的谐波检测原理,分析了自适应神经元算法用于谐波检测的可行性,设计了基于自适应谐波检测的并联型航空混合有源滤波器,对滤波特性进行了仿真研究。结果表明,基于自适应滤波理论的谐波检测方法能够快速、精确地检测相电流谐波含量,在相电压波形发生畸变的情况下,也具有较好的自适应能力、快速补偿能力和跟踪性能。     

An asynchronous recurrent linear threshold network approach to solving the traveling salesman problem

In this paper, an approach to solving the classical Traveling Salesman Problem (TSP) using a recurrent network of linear threshold (LT) neurons is proposed. It maps the classical TSP onto a single-layered recurrent neural network by embedding the constraints of the problem directly into the dynamics of the network. The proposed method differs from the classical Hopfield network in the update of state dynamics as well as the use of network activation function. Furthermore, parameter settings for the proposed network are obtained using a genetic algorithm, which ensure a stable convergence of the network for different problems. Simulation results illustrate that the proposed network performs better than the classical Hopfield network for optimization.     

一种基于脉冲耦合神经网络的语音情感识别新方法

针对汉语语音情感识别问题,提出了一种基于脉冲耦合神经网络(PCNN)的识别方法。该方法将语音转化为语谱图后输入到PCNN,得到输出图像的神经元点火序列及其熵序列作为语音情感的特征,利用其特征实现语音情感识别。实验结果表明,该方法可以有效地识别“高兴”与“平常”这两种不同的情感。该方法将PCNN引入到语音情感识别的应用研究中,开拓了语音和图像信号结合处理的新领域,同时对于PCNN的理论研究和实际应用具有重要的现实意义。     

NMR microscopy of single neurons at 500 MHZ

Previous NMR microimaging studies at 360 MHz have demonstrated a clear differentiation between the nucleus and cytoplasm in isolated single neurons. In particular, theT ₂ of the cell nucleus is 2.5 times larger than that of the cytoplasm. In order to determine the magnitude of possibleT ₂ ^* influences on these observations, images of single cells have been obtained at 500 MHz using spin-echo and line-narrowing sequences. Comparison of the images acquired by the two sequences, and of the spin-echo images at 360 and 500 MHz, imply that anyT ₂ ^* contributions are relatively small. Consequently, the measuredT ₂ differences in spin-echo imaging represent a true difference in theT ₂ relaxation in the two cellular compartments.     

应用Simulink模拟耦合神经元的同步活动

癫痫是一组由神经元异常放电所引起的短暂中枢神经系统功能异常为特征的慢性脑部疾病。其发病的原因正是由于神经元集体的异常同步放电行为所致。以FitzHugh-Nagumo神经元为例,使用simulink对耦合神经元的同步活动进行模拟,供相关研究人员进行研究。