Receptor for Advanced Glycation End Products Upregulation in Cerebral Endothelial Cells Mediates Cerebrovascular ‐related Amyloid β Accumulation after Porphyromonas gingivalis Infection
AbstractCerebrovascular ‐related amyloidogenesis is found in over 80% of Alzheimer’s disease (AD) cases, and amyloid β (Aβ) generation is increased in the peripheral macrophages during infection ofPorphyromonas gingivalis (P. gingivalis), a causal bacterium for periodontitis. In the present study, we focused on receptor for advanced glycation end products (RAGE), the key molecule involves in A β influx afterP. gingivalis infection to test our hypothesis that A β transportation from periphery into the brain, known as “Aβ influx”, is enhanced byP. gingivalis infection. Using cultu...
Source: Journal of Neurochemistry - May 22, 2020 Category: Neuroscience Authors: Fan Zeng, Yicong Liu, Wanyi Huang, Hong Qing, Tomoko Kadowaki, Haruhiko Kashiwazaki, Junjun Ni, Zhou Wu Tags: ORIGINAL ARTICLE Source Type: research

Microglial lysophosphatidic acid promotes glioblastoma proliferation and migration via lpa1 receptor
AbstractGlioblastomas (GBMs) are highly aggressive primary brain tumorscharacterized by cellular heterogeneity, insensitivity to chemotherapy and poor patient survival. Lysophosphatidic acid (LPA) is a lysophospholipidthatacts as a bioactive signaling molecule and plays important roles in diverse biological events during development and disease, including several cancer types. Microglial cells, the resident macrophages ofthe central nervous system,express high levels ofAutotaxin (ATX,Enpp2), an enzymethatsynthetizesLPA. Our study aimed to investigatethe role of LPA on tumor growth and invasion in the context of microglia ...
Source: Journal of Neurochemistry - May 21, 2020 Category: Neuroscience Authors: Rackele Ferreira do Amaral, Luiz Henrique Medeiros Geraldo, Marcelo Einicker ‐Lamas, Tania Cristina Leite de Sampaio e Spohr, Fabio Mendes, Flavia Regina Souza Lima Tags: ORIGINAL ARTICLE Source Type: research

Issue Cover (May 2020)
Front cover:Inhibition of insulin ‐regulated aminopeptidase (IRAP) activity improves spatial working and recognition memory in rodents. However, the mechanism of its cognitive‐enhancing effect remains unknown. There is a close correlation between dendritic spine density and learning in vivo. Dendritic spines are small protrusion s from the dendrites of neurons that serve as contacts with neighboring axons and contain all of the molecular machinery required for synaptic plasticity and long term potentiation, i.e. the storage of memories.Image content: Primary rat hippocampal cultures were exposed to varying concentratio...
Source: Journal of Neurochemistry - May 19, 2020 Category: Neuroscience Tags: Issue Cover Source Type: research

Issue Information
Journal of Neurochemistry, Volume 153, Issue 4, Page 427-432, May 2020. (Source: Journal of Neurochemistry)
Source: Journal of Neurochemistry - May 19, 2020 Category: Neuroscience Tags: Issue Information Source Type: research

Sirtuin 3 is required for the protective effect of Resveratrol on Manganese ‐induced disruption of mitochondrial biogenesis in primary cultured neurons
In conclusion, our findings demo nstrated that RSV could ameliorate Mn‐induced neuronal injury and mitochondrial dysfunction in primary cultured neurons through activating the SIRT1/ PGC‐1α signaling pathway, and that SIRT3 is required for promoting mitochondrial biogenesis and attenuating Mn‐induced mitochondrial dysfunctio n. (Source: Journal of Neurochemistry)
Source: Journal of Neurochemistry - May 19, 2020 Category: Neuroscience Authors: Qian Sun, Run ‐Run Kang, Kai‐Ge Chen, Kuan Liu, Zhuo Ma, Chang Liu, Yu Deng, Wei Liu, Bin Xu Tags: ORIGINAL ARTICLE Source Type: research

Differential mechanisms of tolerance induced by NMDA and 3,5 ‐dihydroxyphenylglycine (DHPG) preconditioning
In conclusion, preconditioning with NMDA or DHPG promotes differential neuroprotective mechanisms: NMDA by internalization of GluA1‐AMPA receptors, DHPG by producing the endocannabinoid 2‐AG. (Source: Journal of Neurochemistry)
Source: Journal of Neurochemistry - May 18, 2020 Category: Neuroscience Authors: Elisabetta Gerace, Elisa Zianni, Elisa Landucci, Tania Scartabelli, Rolando Berlinguer Palmini, Daniela Iezzi, Flavio Moroni, Monica Di Luca, Guido Mannaioni, Fabrizio Gardoni, Domenico E. Pellegrini ‐Giampietro Tags: ORIGINAL ARTICLE Source Type: research

Fluorescence lifetime imaging reveals regulation of presynaptic Ca2+ by glutamate uptake and mGluRs, but not somatic voltage in cortical neurons
AbstractBrain function relies on vesicular release of neurotransmitters at chemical synapses. The release probability depends on action potential ‐evoked presynaptic Ca2+ entry, but also on the resting Ca2+ level. Whether these basic aspects of presynaptic calcium homeostasis show any consistent trend along the axonal path, and how they are controlled by local network activity, remains poorly understood. Here, we take advantage of the recently advanced FLIM ‐based method to monitor presynaptic Ca2+ with nanomolar sensitivity. We find that, in cortical pyramidal neurons, action potential ‐ evoked calcium entry (range ...
Source: Journal of Neurochemistry - May 17, 2020 Category: Neuroscience Authors: Olga Tyurikova, Kaiyu Zheng, Elizabeth Nicholson, Yulia Timofeeva, Alexey Semyanov, Kirill Volynski, Dmitri A. Rusakov Tags: ORIGINAL ARTICLE Source Type: research

HDAC2 (Histone deacetylase 2): a critical factor in environmental enrichment ‐mediated stroke recovery
In this study, focal stroke was induced by photothrombosis in male mice exposing to EE or standard housing (SH) conditions. Recombinant virus vectors, including Ad‐HDAC2‐Flag, AAV‐CAG‐EGFP‐Cre, LV‐shHDAC2 or their controls were microinjected into the motor co rtex at 3 d before stroke. Grid‐walking and cylinder tasks were conducted to assess motor function. Western blot and immunostaining were used to uncover the mechanisms underlying EE‐mediated stroke recovery. We found that EE exposure reversed stroke‐induced HDAC2 upregulation, implicating HDAC 2 in EE‐mediated functional recovery. Importantly, EE...
Source: Journal of Neurochemistry - May 16, 2020 Category: Neuroscience Authors: Yu ‐Hui Lin, Meng‐Cheng Yao, Hai‐Yin Wu, Jian Dong, Huan‐Yu Ni, Xiao‐Lin Kou, Lei Chang, Chun‐Xia Luo, Dong‐Ya Zhu Tags: ORIGINAL ARTICLE Source Type: research

MicroRNA ‐22‐3p alleviates spinal cord ischemia/reperfusion injury by modulating M2 macrophage polarization via IRF5
AbstractCell death after spinal cord ischemia/reperfusion (I/R) can occur through necrosis, apoptosis and autophagy, resulting in changes to the immune environment. However, the molecular mechanism of this immune regulation is not clear. Accumulating evidence indicates that microRNAs (miRs) play a crucial role in the pathogenesis of spinal cord I/R injury. Here, we hypothesized miR ‐22‐3p may be involved in spinal cord I/R injury by interacting with interferon regulatory factor (IRF) 5. Rat models of spinal cord I/R injury were established by 12‐min occlusion of the aortic arch followed by 48‐h reperfusion, with L4...
Source: Journal of Neurochemistry - May 14, 2020 Category: Neuroscience Authors: Hua Fang, Miao Yang, Qin Pan, Hon ‐Ling Jin, Hua‐Feng Li, Ru‐Rong Wang, Quan‐Yun Wang, Jian‐Ping Zhang Tags: ORIGINAL ARTICLE Source Type: research

Role of Sphingolipid Metabolism in Neurodegeneration
AbstractSphingolipids are a class of lipids highly enriched in the central nervous system (CNS), which shows great diversity and complexity, and has been implicated in CNS development and function. Alterations in sphingolipid metabolism have been described in multiple diseases, including those affecting the central nervous system (CNS). In this review, we discuss the role of sphingolipid metabolism in neurodegeneration, evaluating its direct roles in neuron development and health, and also in the induction of neurotoxic activities in CNS ‐resident astrocytes and microglia in the context of neurologic diseases such as mul...
Source: Journal of Neurochemistry - May 13, 2020 Category: Neuroscience Authors: Manal Alaamery, Nour Albesher, Nora Aljawini, Moneera Alsuwailm, Salam Massadeh, Michael A. Wheeler, Chun ‐Cheih Chao, Francisco J. Quintana Tags: REVIEW Source Type: research

Neurochemistry of the K ölliker‐Fuse nucleus from a respiratory perspective
AbstractThe K ölliker‐Fuse nucleus (KF) is a functionally distinct component of the parabrachial complex, located in the dorsolateral pons of mammals. The KF has a major role in respiration and upper airway control. A comprehensive understanding of the KF and its contributions to respiratory function and dysfu nction requires an appreciation for its neurochemical characteristics. The goal of this review is to summarize the diverse neurochemical composition of the KF, focusing on the neurotransmitters, neuromodulators and neuropeptides present. We also include a description of the receptors expressed on KF neurons an...
Source: Journal of Neurochemistry - May 12, 2020 Category: Neuroscience Authors: Adrienn G. Varga, Sebastian N. Maletz, Jordan T. Bateman, Brandon T. Reid, Erica S. Levitt Tags: REVIEW ARTICLE Source Type: research

Protective actions of exercise ‐related FNDC5/Irisin in memory and Alzheimer's disease
AbstractThe proportion of elderly populations is rapidly booming, and human lifespan has considerably increased in the past century due to scientific and medical advances. However, the winds of change brought by the 21st century made sedentarism one of the factors that renders the brain vulnerable to age ‐related chronic diseases, such as Alzheimer's disease (AD). Conversely, physical exercise has been shown to stimulate molecular mechanisms beneficial to cognition. Here, we review evidence showing the positive effects of physical exercise in the brain. We further discuss recent evidence that iris in, a myokine stimulate...
Source: Journal of Neurochemistry - May 12, 2020 Category: Neuroscience Authors: Guilherme B. de Freitas, Mychael V. Lourenco, Fernanda G. De Felice Tags: REVIEW Source Type: research

The uptake of tau amyloid fibrils is facilitated by the cellular prion protein and hampers prion propagation in cultured cells
AbstractTauopathies are prevalent, invariably fatal brain diseases for which no cure is available. Tauopathies progressively affect the brain through cell ‐to‐cell transfer of tau protein amyloids, yet the spreading mechanisms are unknown. Here we show that the cellular prion protein (PrPC) facilitates the uptake of tau aggregates by cultured cells, possibly by acting as an endocytic receptor. In mouse neuroblastoma cells, pull ‐down experiments revealed that tau amyloids bind to PrPC; Confocal images of both wild ‐type and PrPC‐ knockout N2a cells treated with fluorescently labelled synthetic tau fibrils showed ...
Source: Journal of Neurochemistry - May 11, 2020 Category: Neuroscience Authors: Elena De Cecco, Luigi Celauro, Silvia Vanni, Micaela Grandolfo, Edoardo Bistaffa, Fabio Moda, Adriano Aguzzi, Giuseppe Legname Tags: ORIGINAL ARTICLE Source Type: research

What works and what does not work in Alzheimer ’s disease? From interventions on risk factors to anti‐amyloid trials
In this review, we summarize past approaches to finding an anti ‐amyloid‐β monoclonal antibody capable of altering the disease course in Alzheimer's disease (AD). Key learnings from the field have helped shape the current AD clinical development programs, including translating epidemiological observations into potential treatment options, evaluating therapi es across the AD continuum, using biomarkers to assess target engagement and as a surrogate of efficacy, and enriching study populations. Because of the underlying complex pathophysiology of AD, disease‐modifying therapies targeting both amyloid‐dependent a...
Source: Journal of Neurochemistry - May 9, 2020 Category: Neuroscience Authors: Szofia Bullain, Rachelle Doody Tags: REVIEW Source Type: research

Lamina feedback neurons regulate the bandpass property of the flicker ‐induced orientation response in Drosophila
AbstractNatural scenes contain complex visual cues with specific features, including color, motion, flicker and position. It is critical to understand how different visual features are processed at the early stages of visual perception to elicit appropriate cellular responses, and even behavioral output. Here, we studied the visual orientation response induced by flickering stripes in a novel behavioral paradigm inDrosophila melanogaster. We found that free walking flies exhibited bandpass orientation response to flickering stripes of different frequencies. The most sensitive frequency spectrum was confined to low frequenc...
Source: Journal of Neurochemistry - May 8, 2020 Category: Neuroscience Authors: Deliang Yuan, Xiaoxiao Ji, Shun Hao, Julia Gestrich, Wenlan Duan, Xinwei Wang, Yuanhang Xiang, Jihua Yang, Pengbo Hu, Mengbo Xu, Li Liu, Hongying Wei Tags: ORIGINAL ARTICLE Source Type: research

Presynaptic dysfunction in neurodevelopmental disorders: Insights from the synaptic vesicle life cycle
This article will summarise the current state of knowledge linking mutations in presynaptic genes to ne urodevelopmental disorders by sequentially covering the various stages of the synaptic vesicle life cycle. It will also discuss how perturbations of specific stages within this recycling process could translate into human disease. Finally, it will also provide perspectives on the potential for futur e therapy that are targeted to presynaptic function. (Source: Journal of Neurochemistry)
Source: Journal of Neurochemistry - May 7, 2020 Category: Neuroscience Authors: Katherine Bonnycastle, Elizabeth C. Davenport, Michael A. Cousin Tags: REVIEW Source Type: research

Docosahexaenoic acid protection against palmitic acid ‐induced lipotoxicity in NGF differentiated PC12 cells involves enhancement of autophagy and inhibition of apoptosis and necroptosis
ABSTRACTLipotoxicity (LTx) leads to cellular dysfunction and cell death and has been proposed to be an underlying process during traumatic and hypoxic injuries and neurodegenerative conditions in the nervous system. The present study examines cellular mechanisms responsible for docosahexaenoic acid (DHA 22:6 n ‐3) protection in nerve growth factor‐differentiated pheochromocytoma (NGFDPC12) cells from palmitic acid (PAM) mediated lipotoxicity (PAM‐LTx). NGFDPC12 cells exposed to PAM show a significant lipotoxicity demonstrated by a robust loss of cell viability, apoptosis and increased HIF‐1α and BNIP3 gene ex...
Source: Journal of Neurochemistry - May 7, 2020 Category: Neuroscience Authors: Manuel L. Montero, Jo ‐Wen Liu, José Orozco, Carlos A. Casiano, Marino De Leόn Tags: ORIGINAL ARTICLE Source Type: research

Acute pharmacological inhibition of matrix metalloproteinase ‐9 activity during development restores perineuronal net formation and normalizes auditory processing in Fmr1 KO mice
AbstractIndividuals with Fragile X Syndrome (FXS) and autism spectrum disorder (ASD) exhibit cognitive impairments, social deficits, increased anxiety, and sensory hyperexcitability. Previously, we showed that elevated levels of matrix metalloproteinase ‐9 (MMP‐9) may contribute to abnormal development of parvalbumin (PV) interneurons and perineuronal nets (PNNs) in the developing auditory cortex (AC) ofFmr1 knock ‐out (KO) mice, which likely underlie auditory hypersensitivity. Thus, MMP‐9 may serve as a potential target for treatment of auditory hypersensitivity in FXS. Here, we used the MMP‐2/9 inhibitor, SB‐...
Source: Journal of Neurochemistry - May 6, 2020 Category: Neuroscience Authors: Patricia S. Pirbhoy, Maham Rais, Jonathan W. Lovelace, Walker Woodard, Khaleel A. Razak, Devin K. Binder, Iryna M. Ethell Tags: ORIGINAL ARTICLE Source Type: research

The lipid component of Alzheimer ’s disease research
This study highlights the necessity to increase research activities related to lipid metabolism in Alzheimer's disease and demonstrates that the technological progress now facilitates the advancement of this area. (Source: Journal of Neurochemistry)
Source: Journal of Neurochemistry - May 6, 2020 Category: Neuroscience Authors: Lisa Marie Munter Tags: EDITORIAL HIGHLIGHT Source Type: research

Direct dopamine terminal regulation by local striatal microcircuitry
AbstractRegulation of axonal dopamine release by local microcircuitry is at the hub of several biological processes that govern the timing and magnitude of signaling events in reward ‐related brain regions. An important characteristic of dopamine release from axon terminals in the striatum is that it is rapidly modulated by local regulatory mechanisms. These processes can occur via homosynaptic mechanisms ‐ such presynaptic dopamine autoreceptors and dopamine transporters ‐ as well heterosynaptic mechanisms such as retrograde signaling from postsynaptic cholinergic and dynorphin systems, among others. Additionally, m...
Source: Journal of Neurochemistry - April 30, 2020 Category: Neuroscience Authors: Suzanne O. Nolan, Jennifer E. Zachry, Amy R Johnson, Lillian J Brady, Cody A. Siciliano, Erin S. Calipari Tags: REVIEW Source Type: research

Differential mechanisms of tolerance induced by NMDA and DHPG preconditioning
In conclusion, preconditioning with NMDA or DHPG promotes differential neuroprotective me chanisms: NMDA by internalization of GluA1‐AMPA receptors, DHPG by producing the endocannabinoid 2‐AG. (Source: Journal of Neurochemistry)
Source: Journal of Neurochemistry - April 28, 2020 Category: Neuroscience Authors: Elisabetta Gerace, Elisa Zianni, Elisa Landucci, Tania Scartabelli, Rolando Berlinguer Palmini, Daniela Iezzi, Flavio Moroni, Monica Di Luca, Guido Mannaioni, Fabrizio Gardoni, Domenico E. Pellegrini ‐Giampietro Tags: ORIGINAL ARTICLE Source Type: research

Issue Information
Journal of Neurochemistry, Volume 153, Issue 3, Page 291-296, May 2020. (Source: Journal of Neurochemistry)
Source: Journal of Neurochemistry - April 27, 2020 Category: Neuroscience Tags: Issue Information Source Type: research

Issue Cover (May 2020)
Front cover:Ocular microvasculopathies compromise vision in diseases as retinopathy of prematurity and proliferative diabetic retinopathy. Using the oxygen induced retinopathy mouse model, we investigated the effects of aflibercept in modulating the aberrant retinal microvascular response to ischemia.Image content: In this image, a magnified view of a retina from a mouse subjected to the oxygen ‐induced retinopathy protocol and subsequently treated with aflibercept is shown. The tissue was immunolabeled with antibodies against the neural/glial antigen 2 (NG2, red) and the glial fibrillary acidic protein (GFAP, green), wi...
Source: Journal of Neurochemistry - April 27, 2020 Category: Neuroscience Tags: Issue Cover Source Type: research

Cathepsin B inhibition blocks neurite outgrowth in cultured neurons by regulating lysosomal trafficking and remodeling
AbstractLysosomes are known to mediate neurite outgrowth in neurons. However, the principal lysosomal molecule controlling that outgrowth is unclear. We studied primary mouse neuronsin vitro and found that they naturally develop neurite outgrowths over time and as they did so the lysosomal cysteine protease cathepsin B (CTSB) mRNA levels dramatically increased. Surprisingly, we found that treating those neurons with CA ‐074Me, which inhibits CTSB, prevented neurites. As that compound also inhibits another protease, we evaluated a N2a neuronal cell line in which the CTSB gene was deleted (CTSB KO) using CRISPR technology ...
Source: Journal of Neurochemistry - April 24, 2020 Category: Neuroscience Authors: Muzhou Jiang, Jie Meng, Fan Zeng, Hong Qing, Gregory Hook, Vivian Hook, Zhou Wu, Junjun Ni Tags: ORIGINAL ARTICLE Source Type: research

Gut microbiota regulate cognitive deficits and amyloid deposition in a model of Alzheimer ’s disease
AbstractGut microbiota, comprising a vast number of microorganism species with complex metagenome, are known to be associated with Alzheimer ’s disease (AD) and amyloid deposition. However, studies related to gut microbiota have been mostly restricted to comparisons of amyloid deposits, while investigations on neurobehavioral changes and the pathogenesis of AD are limited. Therefore, we aimed to identify the relationship between change s in the intestinal microbiome and the pathogenesis of AD. APPswe/PS1ΔE9 (PAP) transgenic mice and wild type (WT) mice of different age groups were used. The composition of intes...
Source: Journal of Neurochemistry - April 22, 2020 Category: Neuroscience Authors: Zhuo Li, Hua Zhu, Yaxi Guo, Xiaopeng Du, Chuan Qin Tags: ORIGINAL ARTICLE Source Type: research

Amyloid ‐β oligomers in cellular models of Alzheimer’s disease
AbstractAmyloid ‐β (Aβ) dysmetabolism is tightly associated with pathological processes in Alzheimer’s disease (AD). Currently, it is thought that, in addition to Aβ fibrils that give rise to plaque formation, Aβ aggregates into non‐fibrillar soluble oligomers (AβOs). Soluble AβOs have been extensively studied for their synaptotoxic and neurotoxic properties. In this review, we discuss physicochemical properties of AβOs and their impact on different brain cell types in AD. Additionally, we summarize three decades of studies with AβOs, providing a compelling bulk of evidence...
Source: Journal of Neurochemistry - April 22, 2020 Category: Neuroscience Authors: Igor C. Fontana, Aline R. Zimmer, Andreia S. Rocha, Grace Gosmann, Diogo O. Souza, Mychael V. Lourenco, Sergio T. Ferreira, Eduardo R. Zimmer Tags: REVIEW Source Type: research

Issue Information
Journal of Neurochemistry, Volume 153, Issue 2, Page 139-145, April 2020. (Source: Journal of Neurochemistry)
Source: Journal of Neurochemistry - April 21, 2020 Category: Neuroscience Tags: Issue Information Source Type: research

Issue Cover (April 2020)
Front cover:Increasing evidence suggest that the secretome would be an ideal alternative of mesenchymal stem cells (MSCs) transplantation in the treatment of traumatic brain injury (TBI). Transplanted MSCs can sense and response to regeneration signals in the injury microenvironment after TBI. Therefore, it is reasonable to hypothesis that signaling molecules secreted in response to local tissue damage can further promote the therapeutic effect of MSCs secretome. To most closely replicate the complex microenvironment in injured brain, we used extract of traumatic brain tissue to preconditioning umbilical cord mesenchymal s...
Source: Journal of Neurochemistry - April 21, 2020 Category: Neuroscience Tags: Issue Cover Source Type: research

Protective effects of ischemic preconditioning against neuronal apoptosis and dendritic injury in the hippocampus are age ‐dependent
In this study, adult and middle ‐aged male Mongolian gerbils were subjected to nonlethal 5‐min forebrain ischemia (ischemic preconditioning) or sham‐operation, followed by 3 days of reperfusion, and then lethal 15‐min forebrain ischemia. A 9.4‐Tesla MR imaging system was used to study DTI indices, namely fractional aniso tropy (FA), mean diffusivity (MD), and intervoxel coherence (IC) in the hippocampal CA1 and dentate gyrus (DG) areas. In situ expressions of microtubule‐associated protein 2 (MAP2, dendritic marker protein) and apoptosis were also examined. The 5‐min ischemia did not cause dendritic and neuro...
Source: Journal of Neurochemistry - April 21, 2020 Category: Neuroscience Authors: Tsong ‐Hai Lee, Jen‐Tsung Yang, Jr‐Rung Lin, Chaur‐Jong Hu, Wen‐Hai Chou, Ching‐Po Lin, Nai‐Fang Chi Tags: ORIGINAL ARTICLE Source Type: research

Friend or enemy? Review of 17 β‐HSD10 and its role in human health or disease
The objective of this review is to provide a summary about physiological functions and pathological roles of 17β‐HSD10 and the modulators of its activity. (Source: Journal of Neurochemistry)
Source: Journal of Neurochemistry - April 19, 2020 Category: Neuroscience Authors: Lucie Vinklarova, Monika Schmidt, Ondrej Benek, Kamil Kuca, Frank Gunn ‐Moore, Kamil Musilek Tags: REVIEW Source Type: research

PNU ‐120596, a positive allosteric modulator of mammalian α7 nicotinic acetylcholine receptor, is a negative modulator of ligand‐gated chloride‐selective channels of the gastropod Lymnaea stagnalis
Our aim was probing the effects of PNU ‐120596, a positive allosteric modulator (PAM) of α7 nicotinic acetylcholine receptors (nAChR), on the anion‐conducting channels. Experiments were performed onLymnaea stagnalis and rat Purkinje neurons and mammalian receptors expressed inXenopus oocytes or PC12 cells. InLymnaea neurons, PNU ‐120596, contrary to α7 nAChR, inhibited chloride currents mediated by two nAChR subtypes, GABA and glutamate receptors; one nAChR subtype demonstrated a strong acceleration of desensitization. With the mammalian glycine and GABAA receptors, PNU ‐120596 was a weak PAM. Thus, our...
Source: Journal of Neurochemistry - April 19, 2020 Category: Neuroscience Authors: Catherine A. Vulfius, Dmitrii S. Lebedev, Elena V. Kryukova, Denis S. Kudryavtsev, Sergey N. Kolbaev, Yuri N. Utkin, Victor I. Tsetlin Tags: ORIGINAL ARTICLE Source Type: research

Metabolic and perfusion responses to acute hypoglycemia in the rat cortex: a non ‐invasive magnetic resonance approach
AbstractHypoglycemia is critical condition during diabetic treatment that involves intensive insulin therapy, and it may impair brain function. We aimed to compare cortical responses of three hypoglycemic phases and the restoration of glycemia to control levels after a severe episode in rats using non ‐invasive perfusion magnetic resonance (MR) imaging and localised1H MR spectroscopy. Under light a ‐chloralose anaesthesia, cortical blood flow (cCBF) was 42 ± 3 ml/100 g/min at euglycemia (~5 mM plasma glucose), was not altered at mild hypoglycemia I (42 ± 4 ml/100g/min, 2‐3.5mM), increased to 60 ±...
Source: Journal of Neurochemistry - April 19, 2020 Category: Neuroscience Authors: Hongxia Lei, Rolf Gruetter Tags: ORIGINAL ARTICLE Source Type: research

Conformational change and GTPase activity of human tubulin: A comparative study on Alzheimer ’s disease and healthy brain
Axonal microtubule disintegration and neuronal death are characteristics of Alzheimer ’s disease. GTP‐cap which is comprised of GTP‐tubulin is highly important in microtubule dynamic instability. We proposed that in Alzheimer’s disease age‐dependent conformational changes of tubulin causing altered intrinsic tubulin GTPase activity and decreased GTP‐cap length precedes ta u detachment and its subsequent hyperphosphorylation. Human tubulin was purified from normal young adult, normal aged and Alzheimer’s brains. Prolonged lag phase, increased critical concentration and GTPase activity concurrent wi...
Source: Journal of Neurochemistry - April 13, 2020 Category: Neuroscience Authors: Shima Rajaei, Saeed Karima, Hessam Sepasi Tehrani, Somayeh Shateri, Somayeh Mahmoodi Baram, Meisam Mahdavi, Farzad Mokhtari, Alimohammad Alimohammadi, Abbas Tafakhori, Abolfazl Amiri, Vajiheh Aghamollaii, Hamid Fatemi, Masoumeh Rajabibazl, Fa Tags: ORIGINAL ARTICLE Source Type: research

Cross ‐talk between dopamine D1 and corticotropin releasing factor type 2 receptors leads to occlusion of their ERK1/2 signaling
In this study, we further investigated the pharmacological properties of the CRF2α‐D1R heteromer and the consequences of the heteromerization in their signaling and subcellular localization when both receptors are co‐ expressed in HEK293T cells. Using immunoprecipitation assays, we observed that the addition of 10 μM dopamine in the incubation medium significantly decreased the amount of CRF2α on the cell surface of cells expressing both receptors. The presence of agonists of both receptors increased the inter action between CRF2α and D1R as assessed by co‐immunoprecipitation. However, the p...
Source: Journal of Neurochemistry - April 13, 2020 Category: Neuroscience Authors: Hector E. Yarur, Marcela P. Gonz ález, Daniel Verbel‐Vergara, María E. Andrés, Katia Gysling Tags: ORIGINAL ARTICLE Source Type: research

Lipopolysaccharide activates microglia via neuraminidase 1 desialylation of Toll ‐like Receptor 4
AbstractMost cell surface receptors are sialylated, i.e. have sialic acid as the terminal residue of their sugar chains, but can be desialylated by sialidases, such as neuraminidase 1 (Neu1). Desialylation by Neu1 can activate immune cells, such as neutrophils, macrophages and monocytes. We investigated the role of Neu1 in activation of microglia using BV ‐2 cells (a murine microglial cell line) by cytokine ELISAs, enzyme activity assays, antibody/lectin binding and proximity labelling. We found that LPS‐activation caused an increase in Neu1 protein on the cell surface, and an increase in surface sialidase activity tha...
Source: Journal of Neurochemistry - April 12, 2020 Category: Neuroscience Authors: David Hans Allendorf, Elske Helena Franssen, Guy Charles Brown Tags: ORIGINAL ARTICLE Source Type: research

Role of dynein –dynactin complex, kinesins, motor adaptors, and their phosphorylation in dendritogenesis
One of the characteristic features of different classes of neurons is the shape of their dendritic arbors. To properly develop dendritic trees, neurons need to accurately control the intracellular transport of various cellular cargo which relays on motor proteins. This review focuses on the contribution of the dynein –dynactin complex, kinesins, their adaptors, and the phosphorylation of these proteins in dendritogenesis. We review not only the effects of the motor activity of these proteins in dendrites on dendritogenesis but also lesser‐known aspects of their contribution, for example, dynein‐driven axon al tra...
Source: Journal of Neurochemistry - April 12, 2020 Category: Neuroscience Authors: Aleksandra Tempes, Jan Weslawski, Agnieszka Brzozowska, Jacek Jaworski Tags: REVIEW Source Type: research

What works and what doesn ’t work in Alzheimer’s disease? From interventions on risk factors to anti‐amyloid trials
AbstractAlzheimer ’s disease (AD) is a progressive neurodegenerative disorder with no approved disease‐modifying therapy (DMT). In this review, we summarize the various past approaches taken in an attempt to find treatments capable of altering the long‐term course for individuals with AD, including: translating epidemiological observations into potential treatment options; seeking a single treatment approach across the continuum of AD severity; utilizing biomarkers for assessing target engagement; using biomarkers as early surrogates of clinical efficacy; and enriching study populations to demonstrate ade quate p...
Source: Journal of Neurochemistry - April 11, 2020 Category: Neuroscience Authors: Szofia Bullain, Rachelle Doody Tags: REVIEW Source Type: research

Shati/Nat8l deficiency disrupts adult neurogenesis and causes attentional impairment through dopaminergic neuronal dysfunction in the dentate gyrus
AbstractSuccessful completion of daily activities relies on the ability to select the relevant features of the environment for memory and recall. Disruption to these processes can lead to various disorders, such as attention ‐deficit hyperactivity disorder (ADHD). Dopamine is a neurotransmitter implicated in the regulation of several processes, including attention. In addition to the higher‐order brain function, dopamine is implicated in the regulation of adult neurogenesis. Previously, we generated mice lacking Sha ti, an N‐acetyltransferase‐8‐like protein on a C57BL/6J genetic background (Shati/Nat8l−/&mi...
Source: Journal of Neurochemistry - April 10, 2020 Category: Neuroscience Authors: Bolati Wulaer, Kazuo Kunisawa, Kazuhiro Hada, Willy Jaya Suento, Hisayoshi Kubota, Tsubasa Iida, Aika Kosuge, Taku Nagai, Kiyofumi Yamada, Atsumi Nitta, Yasuko Yamamoto, Kuniaki Saito, Akihiro Mouri, Toshitaka Nabeshima Tags: ORIGINAL ARTICLE Source Type: research

Selective inhibition of anti ‐MAG IgM autoantibody binding to myelin by an antigen specific glycopolymer
In conclusion, these observations corroborate the therapeutic potential of PPSGG for an antigen‐specific treatment of an ti‐MAG neuropathy. (Source: Journal of Neurochemistry)
Source: Journal of Neurochemistry - April 9, 2020 Category: Neuroscience Authors: Butrint Aliu, Delphine Demeestere, Emilie Seydoux, Jose Boucraut, Emilien Delmont, Alexandre Brodovitch, Thomas Oberholzer, Shahram Attarian, Marie Th éaudin, Pinelopi Tsouni, Thierry Kuntzer, Tobias Derfuss, Andreas J. Steck, Beat Ernst, R Tags: ORIGINAL ARTICLE Source Type: research

A mechanistic hypothesis for the impairment of synaptic plasticity by soluble A β oligomers from Alzheimer’s brain
This review summarized AD brain ‐derived soluble Aβ oligomers (principally small, diffusible oligomers) could disrupt synaptic plasticity, by binding to membranes and changing excitatory–inhibitory balance, perturbing cellular prion protein and mGluR, down‐regulating glutamate transporters, activating cytokines and associat ed inflammatory mediators, and causing LTP inhibition and LTD facilitation. We synthesize these emerging data into a mechanistic hypothesis for synaptic failure in AD that can be modified as new knowledge is added and specific therapeutics are developed. AbstractIt is increasingly accepte...
Source: Journal of Neurochemistry - April 5, 2020 Category: Neuroscience Authors: Shaomin Li, Dennis J. Selkoe Tags: REVIEW Source Type: research

Extracellular vesicles containing the transferrin receptor as nanocarriers of apotransferrin
AbstractPrevious work by our group has shown the pro ‐differentiating effects of apotransferrin (aTf) on oligodendroglial cellsin vivo andin vitro. Further studies showed the remyelinating effect of aTf in animal demyelination models such as hypoxia/ischemia, where the intranasal administration of human aTf provided brain neuroprotection and reduced white matter damage, neuronal loss and astrogliosis in different brain regions.These data led us to search for a less invasive and controlled technique to deliver aTf to the CNS. To such end, we isolated extracellular vesicles (EVs) from human and mouse plasma and different n...
Source: Journal of Neurochemistry - April 5, 2020 Category: Neuroscience Authors: VS Mattera, P Pereyra Gerber, R Glisoni, M Ostrowski, SV Verstraeten, JM Pasquini, JD Correale Tags: ORIGINAL ARTICLE Source Type: research

NU ‐120596, a Positive Allosteric Modulator of Mammalian α7 Nicotinic Acetylcholine Receptor, is a Negative Modulator of Ligand‐Gated Chloride‐Selective Channels of the Gastropod Lymnaea stagnalis
AbstractExcitatory α7 neuronal nicotinic receptors (nAChR) are widely expressed in the central and peripheral nervous and immune systems and are important for learning, memory and immune response regulation. Specific α7 nAChR ligands, including positive allosteric modulators are promising to treat cognitive disorder s, inflammatory processes and pain. One of them, PNU‐120596, highly increased the neuron response to α7 agonists and retarded desensitization, showing selectivity for α7 as compared to heteromeric nAChRs, but was not examined at the inhibitory ligand‐gated channels. We studied PNU‐...
Source: Journal of Neurochemistry - April 4, 2020 Category: Neuroscience Authors: C.A. Vulfius, D.S. Lebedev, E.V. Kryukova, D.S. Kudryavtsev, S.N. Kolbaev, Yu.N. Utkin, V.I. Tsetlin Tags: ORIGINAL ARTICLE Source Type: research

Termination of acute stress response by the endocannabinoid system is regulated through lysine ‐specific demethylase 1‐mediated transcriptional repression of 2‐AG hydrolases ABHD6 and MAGL
Environmental stress engages physiological responses primed by synaptic activation. In the nucleus direct psychosocial stress effects induce a program of neuroplasticity ‐related gene expression instrumental to memory consolidation of the negative experience. On the behavioral point of view, stress response directly elicits anxiety arousal and increased vigilance. A slower homeostatic response to stress entails nuclear, synaptic, and behavioral adaptations instrum ental to stress response termination. We show that direct targets of LSD1 transcriptional repression at the nuclear level are 2‐AG degrading enzymes ABHD6 an...
Source: Journal of Neurochemistry - March 31, 2020 Category: Neuroscience Authors: Alessandra Longaretti, Chiara Forastieri, Marina Gabaglio, Tiziana Rubino, Elena Battaglioli, Francesco Rusconi Tags: ORIGINAL ARTICLE Source Type: research

SUMOylation controls the neurodevelopmental function of the transcription factor Zbtb20
AbstractSUMOylation is a dynamic post ‐translational protein modification that primarily takes place in cell nuclei, where it plays a key role in multiple DNA‐related processes. In neurons, the SUMOylation‐dependent control of a subset of neuronal transcription factors is known to regulate various aspects of nerve cell differentia tion, development, and function. In an unbiased screen for endogenous SUMOylation targets in the developing mouse brain, based on a His6‐HA‐SUMO1 KI mouse line, we previously identified the transcription factor Zbtb20 as a new SUMO1‐conjugate. We show here that the three key SUMO para...
Source: Journal of Neurochemistry - March 31, 2020 Category: Neuroscience Authors: Silvia Ripamonti, Orr Shomroni, Jeong Seop Rhee, Kamal Chowdhury, Olaf Jahn, Klaus Peter Hellmann, Stefan Bonn, Nils Brose, Marilyn Tirard Tags: ORIGINAL ARTICLE Source Type: research

BDNF deficiency and enriched environment treatment affect neurotransmitter gene expression differently across ages
AbstractDeficiency of activity ‐induced expression of brain‐derived neurotrophic factor BDNF) disturbs neurotransmitter gene expression. Enriched environment treatment (EET) ameliorates the defects. However, how BDNF deficiency and EET affect neurotransmitter gene expression differently across ages remains unclear. We address ed this question by determining neurotransmitter gene expression across three life stages in wild‐type and activity‐dependent BDNF deficient (KIV) mice. Mice received 2‐months of standard control treatment (SCT) or EET at early‐life development (ED: 0–2 months), young adulthood (2&nd...
Source: Journal of Neurochemistry - March 30, 2020 Category: Neuroscience Authors: Brittany E. Dong, Hao Chen, Kazuko Sakata Tags: ORIGINAL ARTICLE Source Type: research

Water ‐Soluble Variant of Human Lynx1 Positively Modulates Synaptic Plasticity and Ameliorates Cognitive Impairment Associated with a7‐nAChR Dysfunction
AbstractLynx1 is a GPI ‐tethered protein colocalized with nicotinic acetylcholine receptors (nAChRs) in the brain areas important for learning and memory. Previously we demonstrated that at low micromolar concentrations the water‐soluble Lynx1 variant lacking GPI‐anchor (ws‐Lynx1) acts on α7‐nAChRs as a positiv e allosteric modulator. We hypothesized that ws‐Lynx1 could be used for improvement of cognitive processes dependent on nAChRs. Here we showed that 2 µM ws‐Lynx1 increased the acetylcholine‐evoked current at α7‐nAChRs in the rat primary visual cortex L1 interneurons. At higher con...
Source: Journal of Neurochemistry - March 30, 2020 Category: Neuroscience Authors: Z.O. Shenkarev, M.A. Shulepko, M.L. Bychkov, D.S. Kulbatskii, O.V. Shlepova, N.A. Vasilyeva, A.A. Andreev ‐Andrievsky, A.S. Popova, E.A. Lagereva, E.V. Loktyushov, S.G. Koshelev, M.S. Thomsen, D.A. Dolgikh, S.A. Kozlov, P.M. Balaban, M.P. Tags: ORIGINAL ARTICLE Source Type: research

Vitamin C regulates Schwann cell myelination by promoting DNA demethylation of pro ‐myelinating genes
AbstractAscorbic acid (vitamin C) is critical for Schwann cells to myelinate peripheral nerve axons during development and remyelination after injury. However, its exact mechanism remains elusive. Vitamin C is a dietary nutrient that was recently discovered to promote active DNA demethylation. Schwann cell myelination is characterized by global DNA demethylationin vivo and may therefore be regulated by vitamin C. We found that vitamin C induces a massive transcriptomic shift (n = 3,848 genes) in primary cultured Schwann cells while simultaneously producing a global increase in genomic 5 ‐hydroxymethylcytosine (5hmC), a D...
Source: Journal of Neurochemistry - March 27, 2020 Category: Neuroscience Authors: Tyler C. Huff, David W. Sant, Vladimir Camarena, Derek Van Booven, Nadja S. Andrade, Sushmita Mustafi, Paula V. Monje, Gaofeng Wang Tags: ORIGINAL ARTICLE Source Type: research

Brain region ‐specific amyloid plaque‐associated myelin lipid loss, APOE deposition and disruption of the myelin sheath in familial Alzheimer’s disease mice
In this study, we examined focal myelin lipid alterations and the disruption of the myelin sheath associated with amyloid plaques in a widely used familial Alzheimer's disease (AD) mouse model; 5xF AD. This AD mouse model has Aβ42 peptide ‐rich plaque deposition in the brain parenchyma. Matrix‐assisted laser desorption/ionization imaging mass spectrometry of coronal brain tissue sections revealed focal Aβ plaque‐associated depletion of multiple myelin‐associated lipid species including sulfatides, galactosylceramides, and sp ecific plasmalogen phopshatidylethanolamines in the hippocampus, cortex, and on t...
Source: Journal of Neurochemistry - March 26, 2020 Category: Neuroscience Authors: Ibrahim Kaya, Eva Jennische, Stefan Lange, Ahmet Tarik Baykal, Per Malmberg, John S. Fletcher Tags: ORIGINAL ARTICLE Source Type: research

Muscone suppresses inflammatory responses and neuronal damage in a rat model of cervical spondylotic myelopathy by regulating Drp1 ‐dependent mitochondrial fission
AbstractCervical spondylotic myelopathy (CSM) is a common cause of disability with few treatments. Aberrant mitochondrial dynamics play a crucial role in the pathogenesis of various neurodegenerative diseases. Thus, regulation of mitochondrial dynamics may offer therapeutic benefit for the treatment of CSM. Muscone, the active ingredient of an odoriferous animal product, exhibits anti ‐inflammatory and neuroprotective effects for which the underlying mechanisms remain obscure. We hypothesized that muscone might ameliorate inflammatory responses and neuronal damage by regulating mitochondrial dynamics. To this end, the ef...
Source: Journal of Neurochemistry - March 26, 2020 Category: Neuroscience Authors: Long ‐yun Zhou, Min Yao, Zi‐rui Tian, Shu‐fen Liu, Yong‐jia Song, Jie Ye, Gan Li, Yue‐li Sun, Xue‐jun Cui, Yong‐jun Wang Tags: ORIGINAL ARTICLE Source Type: research

Crosstalk between dopamine D1 and corticotropin releasing factor type 2 receptors leads to occlusion of their ERK1/2 signaling
AbstractOne manner in which G ‐protein coupled receptors potentiate, increase and change their functionality is through the formation of heteromers in a specific cellular context. Previously, we have shown that dopamine D1 receptor (D1R) and the corticotropin releasing factor receptor type‐2α (CRF2α) heteromerize in HEK293 T cells, enabling D1R to mobilize intracellular calcium in response to D1R agonists. In the present study, we further investigated the pharmacological properties of the CRF2α‐D1R heteromer and the consequences of the heteromerization in their signaling and subcellular localization...
Source: Journal of Neurochemistry - March 26, 2020 Category: Neuroscience Authors: Hector E. Yarur, Marcela P. Gonz ález, Daniel Verbel‐Vergara, María E. Andrés, Katia Gysling Tags: ORIGINAL ARTICLE Source Type: research