The interaction of Synapsin 2a and Synaptogyrin-3 regulates fear extinction in mice.

The mechanisms behind a lack of efficient fear extinction in some individuals are unclear. Here, by employing a principal components analysis-based approach, we differentiated the mice into extinction-resistant and susceptible groups. We determined that elevated synapsin 2a (Syn2a) in the infralimbic cortex (IL) to basolateral amygdala (BLA) circuit disrupted presynaptic orchestration, leading to an excitatory/inhibitory imbalance in the BLA region and causing extinction resistance.

CIP2A deficiency promotes depression-like behaviors in mice through inhibition of dendritic arborization.

Major depressive disorder (MDD) is a severe mental illness. Decreased brain plasticity and dendritic fields have been consistently found in MDD patients and animal models; however, the underlying molecular mechanisms remain to be clarified. Here, we demonstrate that the deletion of cancerous inhibitor of PP2A (CIP2A), an endogenous inhibitor of protein phosphatase 2A (PP2A), leads to depression-like behaviors in mice.

Great Enhancement Effect of 20-40 nm Ag NPs on Solar-Blind UV Response of the Mixed-Phase MgZnO Detector.

High-performance solar-blind UV detector with high response and fast speed is needed in multiple types of areas, which is hard to achieve in one device with a simple structure and device fabrication process. Here, the effects of Ag nanoparticles (NPs) with different sizes on UV response characteristics of the device are studied, the Ag NPs with different sizes that are made from a simple vacuum anneal method. Ag NPs with different sizes could modulate the peak response position of the mixed-phase MgZnO detector from near UV range (350 nm) to deep UV range (235 nm), and the enhancement effect of the Ag NPs on the UV response differs much with the crystal structure and the basic UV response of the MgZnO thin film.

Solar-Blind Photodetector with Lower Dark Current and Higher / Ratio Based on MgZnO Film Deposited by Pulsed Laser Deposition Method.

In this study, pulsed laser deposition method (PLD) was employed to grow MgZnO films on quartz substrates. The optimal deposition temperature of 300 °C for MgZnO film was decided and MgZnO, MgZnO and MgZnO films were grown respectively using MgZnO targets with different Mg contents ( = 0.3, 0.

Direct Activation of Protein Phosphatase 2A (PP2A) by Tricyclic Sulfonamides Ameliorates Alzheimer's Disease Pathogenesis in Cell and Animal Models.

Alzheimer's disease (AD) is a multifactorial neurodegenerative disease for which there are limited therapeutic strategies. Protein phosphatase 2A (PP2A) activity is decreased in AD brains, which promotes the hyperphosphorylation of Tau and APP, thus participate in the formation of neurofibrillary tangles (NFTs) and β-amyloid (Aβ) overproduction. In this study, the effect of synthetic tricyclic sulfonamide PP2A activators (aka SMAPs) on reducing AD-like pathogenesis was evaluated in AD cell models and AD-like hyperhomocysteinemia (HHcy) rat models.

High Sensitivity NO₂ Gas Sensor Based on 3D WO₃ Microflowers Assembled by Numerous Nanoplates.

Tungsten oxide microflowers (WO₃ MFs) were fabricated by a simple hydrothermal process through adjusting the pH of the solution by HCl. These MFs possess the outer diameters of about 2 m and are composed of numerous nanoplates with the average pore size of 10.9 nm.

Solar-Blind Photodetector with Lower Dark Current and Higher / Ratio Based on MgZnO Film Deposited by Pulsed Laser Deposition Method.

In this study, pulsed laser deposition method (PLD) was employed to grow MgZnO films on quartz substrates. The optimal deposition temperature of 300 °C for MgZnO film was decided and MgZnO, MgZnO and MgZnO films were grown respectively using MgZnO targets with different Mg contents ( = 0.3, 0.

Field Emission Properties of Molybdenum Nanoparticles Decorated ZnO Nanorod Arrays.

Precisely controlled dimensions of heterostructured ZnO nanorod arrays were grown on micropatterned Au films supported by Si substrate using chemical vapor deposition (CVD). The field emission properties were attributed to pointed nanorods, thickness of catalyst, preferential growth, density, morphology of ZnO and Molybdenum (Mo) decorated ZnO nanorod arrays (Mo/ZnO). The selective restrained heterostructure approach resulted in excellent control over periodicity, location and density of ZnO nanorod arrays.

CIP2A Causes Tau/APP Phosphorylation, Synaptopathy, and Memory Deficits in Alzheimer's Disease.

Protein phosphatase 2A (PP2A) inhibition causes hyperphosphorylation of tau and APP in Alzheimer's disease (AD). However, the mechanisms underlying the downregulation of PP2A activity in AD brain remain unclear. We demonstrate that Cancerous Inhibitor of PP2A (CIP2A), an endogenous PP2A inhibitor, is overexpressed in AD brain.

Gender-Related Hippocampal Proteomics Study from Young Rats After Chronic Unpredicted Mild Stress Exposure.

Clinical data have shown women are more susceptible to depression. This study was performed to identify differentially regulated proteins from hippocampus in chronic unpredicted mild stress (CUMS)-exposed male and female young rats. After 7 weeks of CUMS, depressed male (M-D) and female rats (F-D) and unstressed male (M-C) and female controls (F-C) were studied.

[A simple method for quantification of tapentadol in dog plasma by liquid chromatography-tandem mass spectrometry and evaluation of the effects of conjugated metabolites on tapentadol].

Tapentadol is a novel drug of opioid pain reliever, which is extensively metabolized primarily through conjugation. Tapentadol glucuronide and tapentadol sulfate are major drug-related metabolites in circulation. The objectives of this study were to develop a simple and rapid method to determine tapentadol and evaluate the effects of conjugated metabolites on tapentadol quantification using liquid chromatography with tandem mass spectrometry in dog plasma.

Infralimbic Endothelin1 Is Critical for the Modulation of Anxiety-Like Behaviors.

Endothelin1 (ET1) is a potent vasoconstrictor that is also known to be a neuropeptide that is involved in neural circuits. We examined the role of ET1 that has been implicated in the anxiogenic process. We found that infusing ET1 into the IL cortex increased anxiety-like behaviors.

Distinct roles of neuregulin in different models of neuropathic pain.

The objective of the study was to investigate the role of neuregulin-ErbB signaling in neuropathic pain in different types of injury. Neuregulin-1(NRG-1) was injected into animals with either formalin-induced pain model or spared nerve injury (SNI) model. Formalin tests or paw withdrawal tests were performed to study the role of NRG-1 in neuropathic pain.

Zinc induces protein phosphatase 2A inactivation and tau hyperphosphorylation through Src dependent PP2A (tyrosine 307) phosphorylation.

The activity of protein phosphatase (PP) 2A is downregulated and promotes the hyperphosphorylation of tau in the brains of Alzheimer's disease (AD), but the mechanism for PP2A inactivation has not been elucidated. We have reported that PP2A phosphorylation at tyrosine 307 (Y307) is involved in PP2A inactivation. Here, we further studied the upstream mechanisms for PP2A phosphorylation and inactivation.

Synaptic released zinc promotes tau hyperphosphorylation by inhibition of protein phosphatase 2A (PP2A).

Hyperphosphorylated tau is the major component of neurofibrillary tangles in Alzheimer disease (AD), and the tangle distribution largely overlaps with zinc-containing glutamatergic neurons, suggesting that zinc released in synaptic terminals may play a role in tau phosphorylation. To explore this possibility, we treated cultured hippocampal slices or primary neurons with glutamate or Bic/4-AP to increase the synaptic activity with or without pretreatment of zinc chelators, and then detected the phosphorylation levels of tau. We found that glutamate or Bic/4-AP treatment caused tau hyperphosphorylation at multiple AD-related sites, including Ser-396, Ser-404, Thr-231, and Thr-205, while application of intracellular or extracellular zinc chelators, or blockade of zinc release by extracellular calcium omission almost abolished the synaptic activity-associated tau hyperphosphorylation.

Lysosomal enzyme cathepsin D protects against alpha-synuclein aggregation and toxicity.

α-synuclein (α-syn) is a main component of Lewy bodies (LB) that occur in many neurodegenerative diseases, including Parkinson's disease (PD), dementia with LB (DLB) and multi-system atrophy. α-syn mutations or amplifications are responsible for a subset of autosomal dominant familial PD cases, and overexpression causes neurodegeneration and motor disturbances in animals. To investigate mechanisms for α-syn accumulation and toxicity, we studied a mouse model of lysosomal enzyme cathepsin D (CD) deficiency, and found extensive accumulation of endogenous α-syn in neurons without overabundance of α-syn mRNA.

AMPA receptor subunit GluR2 gates injurious signals in ischemic stroke.

Ischemic stroke, or a brain attack, is the third leading cause of death in developed countries. A critical feature of the disease is a highly selective pattern of neuronal loss; certain identifiable subsets of neurons--particularly CA1 pyramidal neurons in the hippocampus are severely damaged, whereas others remain intact. A key step in this selective neuronal injury is Ca2+/Zn2+ entry into vulnerable neurons through alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor channels, a principle subtype of glutamate receptors.

[Research on cytokines gene express of rats alcoholic liver disease affected by tea polyphenol].

Objective: To evaluate the effect of tea polyphenol(TP) on the rat with alcoholic liver damage.

Method: Rats were divided into 3 groups, in which 2 groups were stomach perfused with alcohol to result in ALD, and 1 group of them stomach perfused with TP simultaneously. Another group was normal control groups (stomach perfused with drinking water).

Expression of Ca(2+)-permeable AMPA receptor channels primes cell death in transient forebrain ischemia.

CA1 pyramidal neurons degenerate after transient global ischemia, whereas neurons in other regions of the hippocampus remain intact. A step in this selective injury is Ca(2+) and/or Zn(2+) entry through Ca(2+)-permeable AMPA receptor channels; reducing Ca(2+) permeability of AMPA receptors via expression of Ca(2+)-impermeable GluR2(R) channels or activation of CRE transcription in the hippocampus of adult rats in vivo using shutoff-deficient pSFV-based vectors rescues vulnerable CA1 pyramidal neurons from forebrain ischemic injury. Conversely, the induction of Ca(2+) and/or Zn(2+) influx through AMPA receptors by expressing functional Ca(2+)-permeable GluR2(Q) channels causes the postischemic degeneration of hippocampal granule neurons that otherwise are insensitive to ischemic insult.

Activation of cAMP-response-element-binding protein (CREB) after focal cerebral ischemia stimulates neurogenesis in the adult dentate gyrus.

New neurons are generated in adult mammalians and may contribute to repairing the brain after injury. Here, we show that the number of new neurons in the dentate gyrus of adult rats increased in cerebral ischemic stroke and correlated with activation of the cAMP-response-element-binding protein (CREB). Inhibition of endogenous CREB by expression of a dominant-negative mutant of CREB (CREB-S133A or CREB-R287L) blocked ischemia-induced neurogenesis in the dentate gyrus of adult rats, whereas expression of constitutively active CREB, VP16-CREB, increased the number of new neurons.

Cdk5 activation induces hippocampal CA1 cell death by directly phosphorylating NMDA receptors.

CA1 pyramidal neurons degenerate after transient forebrain ischemia, whereas neurons in other regions of the hippocampus remain intact. Here we show that in rat hippocampal CA1 neurons, forebrain ischemia induces the phosphorylation of the N-methyl-D-aspartate (NMDA) receptor 2A subunit at Ser1232 (phospho-Ser1232). Ser1232 phosphorylation is catalyzed by cyclin-dependent kinase 5 (Cdk5).

Interaction of calcineurin and type-A GABA receptor gamma 2 subunits produces long-term depression at CA1 inhibitory synapses.

Long-term depression (LTD) is an activity-dependent weakening of synaptic efficacy at individual inhibitory synapses, a possible cellular model of learning and memory. Here, we show that the induction of LTD of inhibitory transmission recruits activated calcineurin (CaN) to dephosphorylate type-A GABA receptor (GABA(A)Rs) via the direct binding of CaN catalytic domain to the second intracellular domain of the GABA(A)R-gamma(2) subunits. Prevention of the CaN-GABA(A) receptor complex formation by expression of an autoinhibitory domain of CaN in the hippocampus of transgenic mice blocks the induction of LTD.

Generation of functional inhibitory neurons in the adult rat hippocampus.

Several thousand new neurons are produced each day in the adult mammalian hippocampus, among which only excitatory granule cells (GCs) have thus far been identified. In the present study, we used mutant Semliki Forest Virus vectors to express enhanced green fluorescent protein in the hippocampus, and observed that approximately 14% of newly generated neurons in the dentate gyrus of adult rats are GABAergic basket cells (BCs). With the use of double whole-cell patch-clamp recordings from BC-GC pairs in hippocampal slices, we demonstrate that newly generated BCs in the dentate gyrus form inhibitory synapses with principal GCs.

Expression of inducible nitric oxide synthase after focal cerebral ischemia stimulates neurogenesis in the adult rodent dentate gyrus.

The generation of new neurons in the adult mammalian hippocampus is thought to play a role in repairing the brain after injury. Here, we show that 7 d after focal cerebral ischemia, newly divided cells in the dentate gyrus of adult rats increased to approximately sevenfold, compared with sham controls. In the same area, this enhanced dentate neurogenesis was associated with activation of inducible nitric oxide synthase (iNOS).

Gain control of N-methyl-D-aspartate receptor activity by receptor-like protein tyrosine phosphatase alpha.

Src kinase regulation of N-methyl-D-aspartate (NMDA) subtype glutamate receptors in the central nervous system (CNS) has been found to play an important role in processes related to learning and memory, ethanol sensitivity and epilepsy. However, little is known regarding the mechanisms underlying the regulation of Src family kinase activity in the control of NMDA receptors. Here we report that the distal phosphatase domain (D2) of protein tyrosine phosphatase alpha (PTPalpha) binds to the PDZ2 domain of post-synaptic density 95 (PSD95).