Frontostriatal circuit dysfunction leads to cognitive inflexibility in neuroligin-3 R451C knockin mice.

Cognitive and behavioral rigidity are observed in various psychiatric diseases, including in autism spectrum disorder (ASD). However, the underlying mechanism remains to be elucidated. In this study, we found that neuroligin-3 (NL3) R451C knockin mouse model of autism (KI mice) exhibited deficits in behavioral flexibility in choice selection tasks.

GDF11 slows excitatory neuronal senescence and brain ageing by repressing p21.

As a major neuron type in the brain, the excitatory neuron (EN) regulates the lifespan in C. elegans. How the EN acquires senescence, however, is unknown.

NMDA Receptor-Dependent Synaptic Potentiation via APPL1 Signaling Is Required for the Accessibility of a Prefrontal Neuronal Assembly in Retrieving Fear Extinction.

Background: The ventromedial prefrontal cortex has been viewed as a locus for storage and recall of extinction memory. However, the synaptic and cellular mechanisms underlying these processes remain elusive.

Methods: We combined transgenic mice, electrophysiological recording, activity-dependent cell labeling, and chemogenetic manipulation to analyze the role of adaptor protein APPL1 in the ventromedial prefrontal cortex in fear extinction retrieval.

NMDA receptor hypofunction underlies deficits in parvalbumin interneurons and social behavior in neuroligin 3 R451C knockin mice.

Neuroligins (NLs), a family of postsynaptic cell-adhesion molecules, have been associated with autism spectrum disorder. We have reported that dysfunction of the medial prefrontal cortex (mPFC) leads to social deficits in an NL3 R451C knockin (KI) mouse model of autism. However, the underlying molecular mechanism remains unclear.

Variants Associated With Idiopathic Generalized Epilepsies.

The objective of this study is to explore the role of gene in idiopathic generalized epilepsies and the potential underlying mechanism for phenotypic variation. Whole-exome sequencing was performed in a cohort of 88 patients with idiopathic generalized epilepsies. Electro-physiological alterations of the recombinant -methyl-D-aspartate receptors (NMDARs) containing GluN2A mutants were examined using two-electrode voltage-clamp recordings.

Hydrothermal synthesis of a novel nanolayered tin phosphate for removing Cr(iii).

In this work, an outstanding nanolayered tin phosphate with 15.0 Å interlayer spacing, Sn (HPO)·3HO (SnP-H), has been synthesized by conventional hydrothermal method and first used in the adsorptive removal of Cr(iii) from aqueous solution. A number of factors such as contact time, initial concentration of Cr(iii), temperature, pH, and ionic strength on adsorption were investigated by batch tests.

Restoration of Cingulate Long-Term Depression by Enhancing Non-apoptotic Caspase 3 Alleviates Peripheral Pain Hypersensitivity.

Nerve injury in somatosensory pathways may lead to neuropathic pain, which affects the life quality of ∼8% of people. Long-term enhancement of excitatory synaptic transmission along somatosensory pathways contributes to neuropathic pain. Caspase 3 (Casp3) plays a non-apoptotic role in the hippocampus and regulates internalization of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) subunits.

Neuroligin 3 Regulates Dendritic Outgrowth by Modulating Akt/mTOR Signaling.

Neuroligins (NLs) are a group of postsynaptic cell adhesion molecules that function in synaptogenesis and synaptic transmission. Genetic defects in neuroligin 3 (NL3), a member of the NL protein family, are associated with autism. Studies in rodents have revealed that mutations of NL3 gene lead to increased growth and complexity in dendrites in the central nervous system.

Direct Gating of the TRPM2 Channel by cADPR via Specific Interactions with the ADPR Binding Pocket.

cADPR is a well-recognized signaling molecule by modulating the RyRs, but considerable debate exists regarding whether cADPR can bind to and gate the TRPM2 channel, which mediates oxidative stress signaling in diverse physiological and pathological processes. Here, we show that purified cADPR evoked TRPM2 channel currents in both whole-cell and cell-free single-channel recordings and specific binding of cADPR to the purified NUDT9-H domain of TRPM2 by surface plasmon resonance. Furthermore, by combining computational modeling with electrophysiological recordings, we show that the TRPM2 channels carrying point mutations at H1346, T1347, L1379, S1391, E1409, and L1484 possess distinct sensitivity profiles for ADPR and cADPR.

Neuroligins Differentially Mediate Subtype-Specific Synapse Formation in Pyramidal Neurons and Interneurons.

Neuroligins (NLs) are postsynaptic cell-adhesion proteins that play important roles in synapse formation and the excitatory-inhibitory balance. They have been associated with autism in both human genetic and animal model studies, and affect synaptic connections and synaptic plasticity in several brain regions. Yet current research mainly focuses on pyramidal neurons, while the function of NLs in interneurons remains to be understood.

Endocytic Adaptor Protein HIP1R Controls Intracellular Trafficking of Epidermal Growth Factor Receptor in Neuronal Dendritic Development.

Huntington-interacting protein 1-related protein (HIP1R) was identified on the basis of its structural homology with HIP1. Based on its domain structure, HIP1R is a putative endocytosis-related protein. Our previous study had shown that knockdown of HIP1R induces a dramatic decrease of dendritic growth and branching in cultured rat hippocampal neurons.

[Establishment of cardiac remodeling model in FVB/N mice by intraperitoneal injection of isoproterenol].

Objective: To explore the feasibility of intraperitoneal injection of isoproterenol (ISO) to induce cardiac remodeling in FVB/N mice.

Methods: Forty-eight FVB/N mice were divided into back subcutaneous saline group (subcutaneous saline group), intraperitoneal saline group, back subcutaneous ISO group (subcutaneous ISO group), and intraperitoneal ISO group according to the route of administration of saline or ISO. ISO (30 μg/g body weight/day) was given to the subcutaneous ISO group and the intraperitoneal ISO group, twice daily with an interval of 12 hours, for 14 consecutive days.

Gamma Oscillation Dysfunction in mPFC Leads to Social Deficits in Neuroligin 3 R451C Knockin Mice.

Neuroligins (NLs) are critical for synapse formation and function. NL3 R451C is an autism-associated mutation. NL3 R451C knockin (KI) mice exhibit autistic behavioral abnormalities, including social novelty deficits.

A warning for Chinese academic evaluation systems: short-term bibliometric measures misjudge the value of pioneering contributions.

Publication citation-based research evaluation, even if only in support of peer review, is not everywhere, on every level, or for everyone suitable, because of differences in scientific research, patterns of research output, stages of scientific evolution, and merits-scientific or societal-of scientific results.

Removal of chromium(III) from aqueous waste solution by liquid-liquid extraction in a circular microchannel.

A new circular microchannel device has been proposed for the removal of chromium(III) from aqueous waste solution by using kerosene as a diluent and (2-ethylhexyl) 2-ethylhexyl phosphonate as an extractant. The proposed device has several advantages such as a flexible and easily adaptable design, easy maintenance, and cheap setup without the requirement of microfabrication. To study the extraction efficiency and advantages of the circular microchannel device in the removal of chromium(III), the effects of various operating conditions such as the inner diameter of the channel, the total flow velocity, the phase ratio, the initial pH of aqueous waste solution, the reaction temperature and the initial concentration of extractant on the extraction efficiency are investigated and the optimal process conditions are obtained.

Mutations of N-Methyl-D-Aspartate Receptor Subunits in Epilepsy.

Epilepsy is one of the most common neurological diseases. Of all cases, 70%-80% are considered to be due to genetic factors. In recent years, a large number of genes have been identified as being involved in epilepsy.

Functional Investigation of a GRIN2A Variant Associated with Rolandic Epilepsy.

N-methyl-D-aspartate receptors (NMDARs), a subtype of glutamate-gated ion channels, play a central role in epileptogenesis. Recent studies have identified an increasing number of GRIN2A (a gene encoding the NMDAR GluN2A subunit) mutations in patients with epilepsy. Phenotypes of GRIN2A mutations include epilepsy-aphasia disorders and other epileptic encephalopathies, which pose challenges in clinical treatment.

iTRAQ-based Proteomic Analysis of APPSw,Ind Mice Provides Insights into the Early Changes in Alzheimer's Disease.

Background: Several proteins have been identified as potential diagnostic biomarkers in imaging, genetic, or proteomic studies in Alzheimer disease (AD) patients and mouse models. However, biomarkers for presymptom diagnosis of AD are still under investigation, as are the presymptom molecular changes in AD pathogenesis.

Objective: In this study, we aim to analyzed the early proteomic changes in APPSw,Ind mice and to conduct further functional studies on interesting proteins.

Extrasynaptic NMDA receptor dependent long-term potentiation of hippocampal CA1 pyramidal neurons.

In the adult mouse hippocampus, NMDA receptors (NMDARs) of CA1 neurons play an important role in the synaptic plasticity. The location of NMDARs can determine their roles in the induction of long-term potentiation (LTP). However, the extrasynaptic NMDARs (ES-NMDARs) dependent LTP haven't been reported.

Increased Activity of Src Homology 2 Domain Containing Phosphotyrosine Phosphatase 2 (Shp2) Regulates Activity-dependent AMPA Receptor Trafficking.

Long term synaptic plasticity, such as long term potentiation (LTP), has been widely accepted as a cellular mechanism underlying memory. Recently, it has been unraveled that Shp2 plays a role in synaptic plasticity and memory in Drosophila and mice, revealing significant and conserved effects of Shp2 in cognitive function. However, the exact mechanism underlying this function of Shp2 in synaptic plasticity and memory still remains elusive.

Syntabulin regulates the trafficking of PICK1-containing vesicles in neurons.

PICK1 (protein interacting with C-kinase 1) is a peripheral membrane protein that interacts with diverse membrane proteins. PICK1 has been shown to regulate the clustering and membrane localization of synaptic receptors such as AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) receptors, metabotropic glutamate receptor 7, and ASICs (acid-sensing ion channels). Moreover, recent evidence suggests that PICK1 can mediate the trafficking of various vesicles out from the Golgi complex in several cell systems, including neurons.

Detrimental or beneficial: the role of TRPM2 in ischemia/reperfusion injury.

Ischemia/reperfusion (I/R) injury is the main cause of tissue damage and dysfunction. I/R injury is characterized by Ca(2+) overload and production of reactive oxygen species (ROS), which play critical roles in the process of I/R injury to the brain, heart and kidney, but the underlying mechanisms are largely elusive. Recent evidence demonstrates that TRPM2, a Ca(2+)-permeable cationic channel and ROS sensor, is involved in I/R injury, but whether TRPM2 plays a protective or detrimental role in this process remains controversial.