FRET ‐based assay for intracellular evaluation of α‐synuclein aggregation inhibitors
AbstractAggregation of small neuronal protein α-synuclein (αSyn) in amyloid fibrils is considered to be one of the main causes of Parkinson`s disease. Inhibition of this aggregation is a promising approach for the disease treatment. Dozens of compounds able to inhibit αSyn fibrillization in solution were developed during the last decade. How ever, the applicability of most of them in the cellular environment was not established due to the absence of a suitable cell-based assay.In this work, we developed an assay for testing αSyn aggregation inhibitors in cells that is based on fluorescence resonance...
Source: Journal of Neurochemistry - October 23, 2021 Category: Neuroscience Authors: Maksym Galkin, Anastasiia Priss, Oleksandra Topcheva, Dmytro A. Yushchenko, Volodymyr V. Shvadchak Tags: ORIGINAL ARTICLE Source Type: research

Proteostasis deregulation as a driver of C9ORF72 pathogenesis
AbstractAmyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are two related neurodegenerative disorders that display overlapping features. The hexanucleotide repeat expansion GGGGCC (G4C2) inC9ORF72 gene has been causally linked to both ALS and FTD emergence, thus opening a novel potential therapeutic target for disease intervention. A main driver of C9ORF72 pathology is the disruption of distinct cellular processes involved in the function of the proteostasis network. Here we discuss main findings relating the induction of neurodegeneration by C9ORF72 mutation and proteostasis deregulation, highlighting ...
Source: Journal of Neurochemistry - October 22, 2021 Category: Neuroscience Authors: Paulina Torres, Felipe Cabral ‐Miranda, Vicente Gonzalez‐Teuber, Claudio Hetz Tags: REVIEW Source Type: research

Issue Information
Front cover:Mass spectrometry has emerged as a key technology to further our understanding of Alzheimer's disease pathology. The cover image shows mass spectrometry imaging data of amyloid peptides in transgenic mouse brain (tgAPPSwe), as illustrated for the single ion map of A β1-40, showing an amyloid plaque specific localization.Read the full article ‘Preface: Mass spectrometry in Alzheimer disease’ by J. Hanrieder (J. Neurochem. 2021, vol. 159 (2), pp. 207 –210) on doi:10.1111/jnc.15512 (Source: Journal of Neurochemistry)
Source: Journal of Neurochemistry - October 19, 2021 Category: Neuroscience Tags: Issue Information Source Type: research

Preface: Mass spectrometry in Alzheimer disease
Mass spectrometry has emerged as a key technology to further our understanding of Alzheimer disease (AD). In this special issue, key experts present exciting developments and applications of mass spectrometry in the context of studying AD pathology. AbstractThis preface introduces the content of the special issue on ‘Mass Spectrometry in Alzheimer Disease’. Here, an overview is provided on how mass spectrometry is contributing to a broader understanding of AD pathobiology. Mass spectrometry has become a major technology in biomedical analysis and research. This includes biochemical and clinical studies that aim...
Source: Journal of Neurochemistry - October 19, 2021 Category: Neuroscience Authors: J örg Hanrieder Tags: EDITORIAL Source Type: research

Mast cells and histamine are involved in the neuronal damage observed in a quinolinic acid ‐induced model of Huntington's disease
In this study, we aimed to characterize the participation of MCs and HA in the establishment of neural and oxidative damage in the QUIN-induced model of HD. C57BL6/J mice (WT), MC-deficientc-KitW-sh/W-sh (Wsh) mice and Wsh mice reconstituted by intracerebroventricular (i.c.v.) injection of 5 x105 bone marrow-derived mast cells (BMMCs), or i.c.v. administered with HA (5 μg) were used. All groups of animals were intrastriatally injected with 1 μL QUIN (30 nmol/μL) and three days later, apomorphine-induced circling behavior, striatal GABA levels and the number of Fluoro-Jade positive cells, as indicators of neuronal ...
Source: Journal of Neurochemistry - October 19, 2021 Category: Neuroscience Authors: Pablo Eliasib Mart ínez‐Gopar, Marian Jesabel Pérez‐Rodríguez, Gabriela Rodríguez‐Manzo, René Garduño‐Gutierrez, Luis Tristán‐López, Quetzalli Denisse Angeles‐López, Claudia González‐Espinosa, Francisca Pérez‐Severiano Tags: ORIGINAL ARTICLE Source Type: research

The penalty of stress – epichaperomes negatively reshaping the brain in neurodegenerative disorders
AbstractAdaptation to acute and chronic stress and/or persistent stressors is a subject of wide interest in central nervous system disorders. In this context, stress is an effector of change in organismal homeostasis and the response is generated when the brain perceives a potential threat. Herein, we discuss a nuanced and granular view whereby a wide variety of genotoxic and environmental stressors, including aging, genetic risk factors, environmental exposures, and age- and lifestyle-related changes, act as direct insults to cellular, as opposed to organismal, homeostasis. These two concepts of how stressors impact the c...
Source: Journal of Neurochemistry - October 18, 2021 Category: Neuroscience Authors: Stephen D. Ginsberg, Suhasini Joshi, Sahil Sharma, Gianny Guzman, Tai Wang, Ottavio Arancio, Gabriela Chiosis Tags: REVIEW Source Type: research

Withdrawn: MiR ‐132‐3p promotes neuroinflammation and dopaminergic neurodegeneration by suppressing glutaredoxin expression
(Source: Journal of Neurochemistry)
Source: Journal of Neurochemistry - October 17, 2021 Category: Neuroscience Tags: WITHDRAWAL Source Type: research

Glucocerebrosidase 1 and leucine ‐rich repeat kinase 2 in Parkinson disease and interplay between the two genes
AbstractThe glucocerebrosidase 1 gene (GBA1), bi-allelic variants of which cause Gaucher Disease (GD), encodes the lysosomal enzyme glucocerebrosidase (GCase) and is a risk factor for Parkinson Disease (PD). GBA1 variants are linked to a reduction in GCase activity in the brain. Variants in Leucine-Rich Repeat Kinase 2 (LRRK2), such as the gain-of-kinase-function variant G2019S, cause the most common familial form of PD. In patients withoutGBA1 andLRRK2 mutations, GCase and LRRK2 activity are also altered, suggesting that these two genes are implicated in all forms of PD and that they may play a broader role in PD pathogen...
Source: Journal of Neurochemistry - October 8, 2021 Category: Neuroscience Authors: Chiao ‐Yin Lee, Elisa Menozzi, Kai‐Yin Chau, Anthony H V Schapira Tags: REVIEW Source Type: research

Serum beta ‐secretase 1 (BACE1) activity increases in patients with mild cognitive impairment
Beta-secretase 1 (BACE1) plays a central role in the production of amyloid- β in Alzheimer disease. BACE1 increase in brain and serum is associated with the occurrence of AD. This change occurs already in mild cognitive impairment (MCI) patients. Therefore, we evaluated whether serum BACE1 activity increases in MCI patients and is associated with the progression from MCI t o dementia. Or findings showed significantly increased serum BACE1 activity in MCI patients (both amnestic and non-amnestic) compared with Controls, and overall suggest that a dysregulation of this enzyme might be an early event primarily associated...
Source: Journal of Neurochemistry - October 4, 2021 Category: Neuroscience Authors: Giovanni Zuliani, Alessandro Trentini, Gloria Brombo, Valentina Rosta, Patrizia Guasti, Tommaso Romagnoli, Michele Polastri, Lisa Marabini, Dario Pedrini, Chiara Pistolesi, Salvatore Pacifico, Remo Guerrini, Davide Seripa, Carlo Cervellati Tags: ORIGINAL ARTICLE Source Type: research

Synaptotagmin ‐11 inhibits spontaneous neurotransmission through vti1a
AbstractRecent work has revealed that spontaneous release plays critical roles in the central nervous system, but how it is regulated remains elusive. Here we report that synaptotagmin-11 (Syt11), a Ca2+-independent Syt isoform associated with schizophrenia and Parkinson ’s disease, suppressed spontaneous release. Syt11-knockout hippocampal neurons showed an increased frequency of miniature excitatory postsynaptic currents while overexpression of Syt11 inversely decreased the frequency. Neither knockout nor overexpression of Syt11 affected the average amplitude, s uggesting the presynaptic regulation of spontaneous n...
Source: Journal of Neurochemistry - October 2, 2021 Category: Neuroscience Authors: Wan ‐Ru Li, Ya‐Long Wang, Chao Li, Pei Gao, Fei‐Fan Zhang, Meiqin Hu, Jing‐Chen Li, Shuli Zhang, Rena Li, Claire Xi Zhang Tags: ORIGINAL ARTICLE Source Type: research

Glucose availability limits microglial nitric oxide production
ABSTRACTMetabolic intermediates influence inflammation not only through signaling effects, but also by fueling production of pro-inflammatory molecules. Microglial production of nitric oxide (NO) requires consumption of NADPH. NADPH consumed in this process is regenerated from NADP+ primarily through the hexose monophosphate shunt, which can utilize only glucose as a substrate. These factors predict that glucose availability can be rate-limiting for glial NO production. To test this prediction, cultured astrocytes and microglia were incubated with lipopolysaccharide and interferon- γ to promote expression of inducibl...
Source: Journal of Neurochemistry - September 30, 2021 Category: Neuroscience Authors: Erika Castillo, Ebony Mocanu, G ӧkhan Uruk, Raymond A. Swanson Tags: ORIGINAL ARTICLE Source Type: research

Issue Information
Front cover:Autism Spectrum Disorder (ASD) is a neurodevelopmental disease originating from combined genetic and environmental factors. Post-mortem human studies and some animal ASD models have shown brain neuroinflammation, oxidative stress and changes in blood brain barrier (BBB) integrity. The balance between Wnt- β-catenin and Shh pathways controls angiogenesis, barriergenesis, neurodevelopment, central nervous system (CNS) morphogenesis and neuronal guidance. These interactions are critical to maintain BBB function in the mature CNS to prevent influx of pathogens and inflammatory cells. Dysregulation of th e Soni...
Source: Journal of Neurochemistry - September 29, 2021 Category: Neuroscience Tags: Issue Information Source Type: research

The metabolite GLP ‐1 (9‐36) is neuroprotective and anti‐inflammatory in cellular models of neurodegeneration
AbstractGlucagon-like peptide-1 (GLP-1) is best known for its insulinotropic action following food intake. Its metabolite, GLP-1 (9-36), was assumed biologically inactive due to low GLP-1 receptor (GLP-1R) affinity and non-insulinotropic properties; however, recent studies contradict this assumption. Increased use of FDA approved GLP-1 analogues for treating metabolic disorders and neurodegenerative diseases raises interest in GLP-1 (9-36) ’s biological role. We use human SH-SY5Y neuroblastoma cells and a GLP-1R overexpressing variety (#9), in both undifferentiated and differentiated states, to evaluate the neurotrop...
Source: Journal of Neurochemistry - September 27, 2021 Category: Neuroscience Authors: Yazhou Li, Elliot J. Glotfelty, Tobias Karlsson, Lowella V. Fortuno, Brandon K. Harvey, Nigel H. Greig Tags: ORIGINAL ARTICLE Source Type: research

Antimicrobial Protein REG3A and Signaling Networks are Predictive of Stroke Outcomes
AbstractRegenerating Family Member 3 Alpha (REG3A) is a multifunctional protein with antimicrobial activity, and primarily secreted by the intestine and pancreas. Studies have shown an increased expression of REG3A in systemic inflammatory responses to acute injury and infection, but studies investigating REG3A during the pathogenesis of ischemic stroke are limited. The aims of this study were to examine the associations between arterial expression of REG3A and other arterial inflammatory proteins implicated in stroke pathogenesis, as well as associations between REG3A and markers of poor outcome for ischemic stroke. The U...
Source: Journal of Neurochemistry - September 24, 2021 Category: Neuroscience Authors: Madison Sands, Jacqueline A. Frank, Benton Maglinger, Christopher J. McLouth, Amanda L. Trout, Jadwiga Turchan ‐Cholewo, Ann M. Stowe, Justin F. Fraser, Keith R. Pennypacker Tags: ORIGINAL ARTICLE Source Type: research

Ferroptosis as a mechanism of neurodegeneration in Alzheimer's disease
AbstractAlzheimer's disease (AD) is the most prevalent form of dementia, with complex pathophysiology that is not fully understood. While β-amyloid plaque and neurofibrillary tangles define the pathology of the disease, the mechanism of neurodegeneration is uncertain. Ferroptosis is an iron-mediated programmed cell death mechanism characterised by phospholipid peroxidation that has been observed in clinical AD samples. This review wi ll outline the growing molecular and clinical evidence implicating ferroptosis in the pathogenesis of AD, with implications for disease-modifying therapies. (Source: Journal of Neurochemistry)
Source: Journal of Neurochemistry - September 23, 2021 Category: Neuroscience Authors: Md. Jakaria, Abdel Ali Belaidi, Ashley I. Bush, Scott Ayton Tags: REVIEW Source Type: research

Issue Information
Front cover:Sacral modulation of lumbar motor output. Stimulation of sacrocaudal afferents, is a powerful initiator and modulator of the locomotor rhythm in the isolated spinal cord of newborn rodents. This stimulation activates sacral relay neurons that project via the ventral funiculi (VF) to lumbar motoneurons and to the locomotor networks. Mono/oligo synaptic connectivity between some of the sacral VF neurons and lumbar motoneurons is proposed to regulate the motor output, initiated by sacrocaudal afferents stimulation, and contribute to its cholinergic modulation (e.g. Matzner et al., this issue).The existence of this...
Source: Journal of Neurochemistry - September 22, 2021 Category: Neuroscience Tags: Issue Information Source Type: research

Reviewers List
(Source: Journal of Neurochemistry)
Source: Journal of Neurochemistry - September 22, 2021 Category: Neuroscience Tags: ACKNOWLEDGEMENT OF REVIEWERS Source Type: research

Cerebrospinal fluid levels of L ‐glutamate signal central inflammatory neurodegeneration in multiple sclerosis
ABSTRACTExcessive extracellular concentrations of L-glutamate (L-Glu) can be neurotoxic and contribute to neurodegenerative processes in multiple sclerosis (MS).The association between cerebrospinal fluid (CSF) L-Glu levels, clinical features, and inflammatory biomarkers in patients with MS remains unclear.In 179 MS patients (relapsing remitting, RR, n = 157; secondary progressive/primary progressive, SP/PP, n = 22), CSF levels of L-Glu at diagnosis were determined and compared with those obtained in a group of 40 patients with non-inflammatory/non-degenerative disorders. Disability at the time of diagnosis, and after 1 ye...
Source: Journal of Neurochemistry - September 21, 2021 Category: Neuroscience Authors: Mario Stampanoni Bassi, Tommaso Nuzzo, Luana Gilio, Mattia Miroballo, Alessia Casamassa, Fabio Buttari, Paolo Bellantonio, Roberta Fantozzi, Giovanni Galifi, Roberto Furlan, Annamaria Finardi, Arianna De Rosa, Anna Di Maio, Francesco Errico, Tags: ORIGINAL ARTICLE Source Type: research

EFhd2 brain interactome reveals its association with different cellular and molecular processes
This study presents, for the first time, an EFhd2 brain interactome that it is associated with different cellular and molecular processes.These findings will help prioritize further studies to investigate the mechanisms by which EFhd2 modulates these processes in physiological and pathological conditions of the nervous system. (Source: Journal of Neurochemistry)
Source: Journal of Neurochemistry - September 20, 2021 Category: Neuroscience Authors: Ahlam S. Soliman, Andrew Umstead, Tessa Grabinski, Nicholas M. Kanaan, Andy Lee, John Ryan, Jared Lamp, Irving E. Vega Tags: ORIGINAL ARTICLE Source Type: research

Molecular signatures from multi ‐omics of autism spectrum disorders and schizophrenia
AbstractThe genetic and phenotypic heterogeneity of autism spectrum disorder (ASD) impedes the unification of multiple biological hypotheses in an attempt to explain the complex features of ASD, such as impaired social communication, social interaction deficits, and restricted and repetitive patterns of behavior. However, recent psychiatric genetic studies have identified numerous risk genes and chromosome loci (copy number variation: CNV) which enable us to analyze at the single gene level and utilize system-level approaches. In this review, we focus on ASD as a major neurodevelopmental disorder and review recent findings...
Source: Journal of Neurochemistry - September 19, 2021 Category: Neuroscience Authors: Jun Nomura, Matthew Mardo, Toru Takumi Tags: REVIEW Source Type: research

Serum Beta Secretase 1 (BACE1) activity increases in patients with mild cognitive impairment
AbstractBeta-secretase1 (BACE1) is considered as the key-enzyme in amyloid- β formation. Previous works suggest that high BACE1 activity may be present in brain, cerebrospinal fluid and serum of patients with late-onset Alzheimer’s disease (LOAD) as well as mild cognitive impairment (MCI).Therefore, we evaluated whether serum BACE1 activity increases in MCI patients and is associated with the progression from MCI to dementia.BACE1 activity was measured in the serum of 259 MCI patients (162 amnestic – aMCI, 97 non-amnestic - naMCI) and 204 healthy Controls. After a median follow-up of 32 months (range: 10-1...
Source: Journal of Neurochemistry - September 18, 2021 Category: Neuroscience Authors: Giovanni Zuliani, Alessandro Trentini, Gloria Brombo, Valentina Rosta, Patrizia Guasti, Tommaso Romagnoli, Michele Polastri, Lisa Marabini, Dario Pedrini, Chiara Pistolesi, Salvatore Pacifico, Remo Guerrini, Davide Seripa, Carlo Cervellati Tags: ORIGINAL ARTICLE Source Type: research

The Role of Neuroimaging in Parkinson ’s Disease
AbstractParkinson ’s disease (PD) is a neurodegenerative disorder that affects millions of people worldwide. Two hallmarks of PD are the accumulation of alpha-synuclein and the loss of dopaminergic neurons in the brain. There is no cure for PD, and all existing treatments focus on alleviating the symptoms. PD diagn osis is also based on the symptoms, such as abnormalities of movement, mood and cognition observed in the patients.Molecular imaging methods such as magnetic resonance imaging (MRI), single photon emission computed tomography (SPECT) and positron emission tomography (PET) can detect objective alterations i...
Source: Journal of Neurochemistry - September 17, 2021 Category: Neuroscience Authors: Natasha Bidesi, Ida Vang Andersen, Albert D. Windhorst, Vladimir Shalgunov, Matthias M. Herth Tags: REVIEW Source Type: research

Pharmacological preconditioning by TERT inhibitor BIBR1532 confers neuronal ischemic tolerance through TERT ‐mediated transcriptional reprogramming
AbstractAfter a sublethal ischemic preconditioning (IPC) stimulus, the brain has a remarkable capability of acquiring tolerance to subsequent ischemic insult by establishingprecautionary self-protective mechanism. Understanding this endogenous mechanism would reveal novel and effective neuroprotective targets for ischemic brain injury. Our previous study has implied that telomerase reverse transcriptase (TERT) is associated with IPC-induced tolerance. Here, we investigated the mechanism of TERT-mediated ischemic tolerance. Preconditioning was modeled by oxygen-glucose deprivation (OGD) and by TERT inhibitor BIBR1532 in pri...
Source: Journal of Neurochemistry - September 17, 2021 Category: Neuroscience Authors: Xuemin Xie, Mingxi Li, Mengyao Zhou, Shing Fung Chow, Chi Kwan Tsang Tags: ORIGINAL ARTICLE Source Type: research

Investigating the molecular mechanisms of learning and memory using Caenorhabditis elegans
AbstractLearning is an essential biological process for survival since it facilitates behavioural plasticity in response to environmental changes. This process is mediated by a wide variety of genes, mostly expressed in the nervous system. Many studies have extensively explored the molecular and cellular mechanisms underlying learning and memory. This review will focus on the advances gained through the study of the nematodeCaenorhabditis elegans.C. elegans provides an excellent system to study learning due to its genetic tractability, in addition to its invariant, compact nervous system (~300 neurons) that is well-charact...
Source: Journal of Neurochemistry - September 16, 2021 Category: Neuroscience Authors: Aelon Rahmani, Yee Lian Chew Tags: REVIEW Source Type: research

Central sympathetic nerve activation in subarachnoid hemorrhage
AbstractSubarachnoid hemorrhage (SAH) is a life-threatening condition, and although its two main complications —cerebral vasospasm (CVS)/delayed cerebral ischemia (DCI) and early brain injury (EBI)—have been widely studied, prognosis has not improved over time. The sympathetic nerve (SN) system is important for regulating cardiovascular function and is closely associated with cerebral vessels and the reg ulation of cerebral blood flow and cerebrovascular function; thus, excessive SN activation leads to a rapid breakdown of homeostasis in the brain. In the hyperacute phase, patients with SAH can experience possi...
Source: Journal of Neurochemistry - September 16, 2021 Category: Neuroscience Authors: Yu Hasegawa, Hiroki Uchikawa, Sosho Kajiwara, Motohiro Morioka Tags: REVIEW Source Type: research

From Psychiatry to Neurology: Psychedelics as Prospective Therapeutics for Neurodegenerative Disorders
AbstractThe studies of psychedelics, especially psychedelic tryptamines like psilocybin, are rapidly gaining interest in neuroscience research. Much of this interest stems from recent clinical studies demonstrating that they have a unique ability to improve the debilitating symptoms of major depressive disorder (MDD) long-term after only a single treatment. Indeed, the Food and Drug Administration (FDA) has recently designated two Phase III clinical trials studying the ability of psilocybin to treat forms of MDD with "Breakthrough Therapy" status. If successful, the use of psychedelics to treat psychiatric diseas...
Source: Journal of Neurochemistry - September 14, 2021 Category: Neuroscience Authors: Urszula Kozlowska, Charles Nichols, Kalina Wiatr, Maciej Figiel Tags: REVIEW ARTICLE Source Type: research

Synaptophysin ‐dependent synaptobrevin‐2 trafficking at the presynapse‐Mechanism and function
Synaptophysin (Syp) is the second most abundant protein on synaptic vesicles at the presynapse, however its physiological role has remained elusive. This review summarises proposed roles of Syp, and proposes that its sole function is to control the endocytic retrieval of synaptobrevin-2 (Syb2). It also provides a unifying model, outlining how Syp directs Syb2 trafficking in collaboration with other key players such as intersectin-1 and adaptor protein 180 (AP180)/clathrin assembly lymphoid myeloid leukaemia (CALM). The review concludes with a series of perspectives and unaddressed questions relating to Syp-dependent Syb2 t...
Source: Journal of Neurochemistry - September 10, 2021 Category: Neuroscience Authors: Michael A. Cousin Tags: REVIEW ARTICLE Source Type: research

Morphine ‐induced kinase activation and localization in the periaqueductal gray of male and female mice
AbstractMorphine is a potent opioid analgesic with high propensity for the development of antinociceptive tolerance. Morphine antinociception and tolerance are partially regulated by the midbrain ventrolateral periaqueductal gray (vlPAG). However, the majority of research evaluating mu-opioid receptor signaling has focused on males. Here, we investigate kinase activation and localization patterns in the vlPAG following acute and chronic morphine treatment in both sexes. Male and female mice developed rapid antinociceptive tolerance to morphine (10 mg/kg i.p.) on the hot plate assay, but tolerance did not develop in males o...
Source: Journal of Neurochemistry - September 9, 2021 Category: Neuroscience Authors: Akila Ram, Taylor M. Edwards, Ashley McCarty, Max V. McDermott, Erin N. Bobeck Tags: ORIGINAL ARTICLE Source Type: research

Targeting focal ischemic and hemorrhagic stroke neuroprotection: current prospects for local hypothermia
AbstractTherapeutic hypothermia (TH) has applications dating back millennia. In modern history, however, TH saw its importation into medical practice where investigations have demonstrated that TH is efficacious in ischemic insults, notably cardiac arrest and hypoxic-ischemic encephalopathy. As well, studies have been undertaken to investigate whether TH can provide benefit in focal stroke (i.e., focal ischemia and intracerebral hemorrhage). However, clinical studies have encountered various challenges with induction and maintenance of post-stroke TH. Most clinical studies have attempted to use body-wide cooling protocols,...
Source: Journal of Neurochemistry - September 9, 2021 Category: Neuroscience Authors: Lane J. Liddle, Anna C.J. Kalisvaart, Ashley H. Abrahart, Mohammed Almekhlafi, Andrew Demchuk, Frederick Colbourne Tags: REVIEW Source Type: research

Transient expansion of the expression region of Hsd11b1, encoding 11 β‐hydroxysteroid dehydrogenase type 1, in the developing mouse neocortex
AbstractCorticosteroids are stress-related hormones that maintain homeostasis. The most effective corticosteroids are corticosterone (CORT) in rodents and cortisol in primates. 11 β-Hydroxysteroid dehydrogenase type 1 (11β-HSD1; EC 1.1.1.146), encoded byHsd11b1, is a key regulator of the local concentration of CORT/cortisol.Hsd11b1 expression in layer 5 of the primary somatosensory cortex has been shown in adult mice. However, its localization in the entire neocortex, especially during development, has not been fully addressed. Here, we established robust and dynamic expression profiles ofHsd11b1 in the developin...
Source: Journal of Neurochemistry - September 8, 2021 Category: Neuroscience Authors: Miyuki Doi, Yuichiro Oka, Manabu Taniguchi, Makoto Sato Tags: ORIGINAL ARTICLE Source Type: research

Palmitate ‐mediated induction of neuropeptide Y expression occurs through intracellular metabolites and not direct exposure to proinflammatory cytokines
This study suggests that the intracellular metabolism of palmitate and elevation of metabolites, including ceramide and phospholipids, are responsible for the palmitate-mediated induction of the potent orexigenNpy. Furthermore, this suggests that the regulation ofNpy expression is less reliant on inflammatory cytokinesper se than palmitate metabolites in a model of NPY/AgRP neurons. These lipid species likely induce detrimental downstream cellular signalling events ultimately causing an increase in feeding, resulting in an overweight phenotype and/or obesity. (Source: Journal of Neurochemistry)
Source: Journal of Neurochemistry - September 6, 2021 Category: Neuroscience Authors: Andy Tran, Wenyuan He, Jim T.C. Chen, Leigh Wellhauser, Kathyrn E. Hopperton, Richard P. Bazinet, Denise D. Belsham Tags: ORIGINAL ARTICLE Source Type: research

Neurosteroids: a novel promise for the treatment of stroke and post ‐stroke complications
AbstractStroke is the primary reason for death and disability worldwide, with few treatment strategies to date. Neurosteroids, which are natural molecules in the brain, have aroused great interest in the field of stroke. Neurosteroids are a kind of steroid that acts on the nervous system, and are synthesized in the mitochondria of neurons or glial cells using cholesterol or other steroidal precursors. Neurosteroids mainly include estrogen, progesterone (PROG), allopregnanolone, dehydroepiandrosterone (DHEA), and vitamin D (VD). Most of the preclinical studies have confirmed that neurosteroids can decrease the risk of strok...
Source: Journal of Neurochemistry - September 5, 2021 Category: Neuroscience Authors: Jiawei Xu, Yunxiang Zhou, Caochong Yan, Xiaoyu Wang, Jianyao Lou, Yi Luo, Shiqi Gao, Junjie Wang, Liang Wu, Xiangfu Gao, Anwen Shao Tags: REVIEW ARTICLE Source Type: research

Does the inability of CA1 area to respond to ischemia with early rapid adenosine release contribute to hippocampal vulnerability?
This Editorial highlights a remarkable study in the current issue of the Journal of Neurochemistry in which Ganesana and Venton (2021) report new data showing that brain ischemia does not elicit transient adenosine release in the CA1  hippocampal area. Using fast-scan cyclic voltammetry at a carbon-fiber microelectrode implanted in the CA1 subfield of the hippocampus, it was shown that none of three different ischemia/reperfusion models could increase spontaneous, transient adenosine release, and more severe models even suppre ssed this presumably neuroprotective release. Since the authors have previously shown t...
Source: Journal of Neurochemistry - September 4, 2021 Category: Neuroscience Authors: Natalia V. Gulyaeva Tags: EDITORIAL HIGHLIGHT Source Type: research

The drebrin/EB3 pathway regulates cytoskeletal dynamics to drive neuritogenesis in embryonic cortical neurons
AbstractCo-ordinating the dynamic behaviour of actin filaments (F-actin) and microtubules in filopodia is an important underlying process in neuritogenesis but the molecular pathways involved are ill-defined. The drebrin/end-binding protein 3 (EB3) pathway is a candidate pathway for linking F-actin to microtubules in filopodia. Drebrin binds F-actin and, simultaneously, the microtubule-binding protein EB3 when bound to microtubule plus-ends. We assessed the effect on neuritogenesis of gain- or loss-of-function of proteins in the drebrin/EB3 pathway in rat embryonic cortical neurons in culture. Loss-of-function of drebrin b...
Source: Journal of Neurochemistry - September 3, 2021 Category: Neuroscience Authors: Thanushiyan Poobalasingam, Francesca Bianco, Fazal Oozeer, Phillip R. Gordon ‐Weeks Tags: ORIGINAL ARTICLE Source Type: research

Kappa free light chain index as a diagnostic biomarker in multiple sclerosis: a real ‐world investigation
AbstractKappa free light chain (KFLC)-index, a measure for intrathecal production of free kappa chains, has been increasingly recognized for its diagnostic potential in multiple sclerosis (MS) as a quantitative alternative to IgG oligoclonal-bands (OCBs). Our objective was to investigate the sensitivity, specificity, and overall diagnostic accuracy of KFLC-index in MS. KFLC-index was prospectively determined as part of the diagnostic workup in patients with suspected MS (n=327) between May 2013 and February 2020. Patients with clinically isolated syndrome (CIS), radiologically isolated syndrome (RIS), and MS had markedly h...
Source: Journal of Neurochemistry - September 3, 2021 Category: Neuroscience Authors: Igal Rosenstein, Sofia Rasch, Markus Axelsson, Lenka Novakova, Kaj Blennow, Henrik Zetterberg, Jan Lycke Tags: ORIGINAL ARTICLE Source Type: research

Criss ‐crossing Autism Spectrum Disorder and Adult Neurogenesis
AbstractAutism spectrum disorder (ASD) comprises a group of multifactorial neurodevelopmental disorders primarily characterized by deficits in social interaction and repetitive behavior. Although the onset is typically in early childhood, ASD poses a life-long challenge for both patients and caretakers. Adult neurogenesis (AN) is the process by which new functional neurons are created from neural stem cells existing in the postnatal brain. The entire event is based on a sequence of cellular processes such as proliferation, specification of cell fate, maturation and, ultimately, synaptic integration into the existing neural...
Source: Journal of Neurochemistry - September 3, 2021 Category: Neuroscience Authors: Frank Bicker, Leonardo Nardi, Jannik Maier, Verica Vasic, Michael J. Schmeisser Tags: REVIEW Source Type: research

Amyloid pathology and synaptic loss in pathological aging
In this study, we investigated and compared synaptic protein levels, amyloid plaque load, and Aβ peptide patterns between AD and PA. Two cohorts of post-mortem brain tissue were investigated. In the first, consisting of controls, PA, AD, and familial AD (FAD) individuals, synapti c proteins extracted with tris(hydroxymethyl)aminomethane-buffered saline (TBS) were analyzed. In the second, consisting of tissue from AD and PA patients from three different regions (occipital lobe, frontal lobe, and cerebellum), a two-step extraction was performed. Five synaptic proteins were ext racted using TBS, and from the remaining po...
Source: Journal of Neurochemistry - September 3, 2021 Category: Neuroscience Authors: Eleni Gkanatsiou, Johanna Nilsson, Christina E. Toomey, Agathe Vrillon, Hlin Kvartsberg, Erik Portelius, Henrik Zetterberg, Kaj Blennow, Ann Brinkmalm, Tammaryn Lashley, Gunnar Brinkmalm Tags: ORIGINAL ARTICLE Source Type: research

Synaptophysin ‐dependent synaptobrevin‐2 trafficking at the presynapse ‐ mechanism and function
AbstractSynaptobrevin-2 (Syb2) is a soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) that is essential for neurotransmitter release. It is the most numerous protein on a synaptic vesicle (SV) and drives SV fusion via interactions with its cognate SNARE partners on the presynaptic plasma membrane. Synaptophysin (Syp) is the second most abundant protein on SVs, however in contrast to Syb2 it has no obligatory role in neurotransmission. Syp interacts with Syb2 on SVs, and the molecular nature of its interaction with Syb2 and its physiological role has been debated for decades. However, recent stud...
Source: Journal of Neurochemistry - September 1, 2021 Category: Neuroscience Authors: Michael A. Cousin Tags: REVIEW ARTICLE Source Type: research

MEC17 ‐induced α‐tubulin acetylation restores mitochondrial transport function and alleviates axonal injury after intracerebral hemorrhage in mice
In this study, we found that microtubule disassembly induced mitochondrial transport dysfunction and mitochondrial dysfunction were initial events for axonal injury, and acetylated α-tubulin (α-Ac-Tub) and mitochondrial permeability transition pore (mPTP) were promising therapeutic targets. We enhanced the availability of α-Ac-Tub using tubsatatin A (TubA), ablated α-Ac-Tub usingMEC17−/− mice and inhibited mPTP opening with cyclosporin A (CsA). The results indicated MEC17 ablation aggravated the axonal injury and combined treatment with TubA and CsA at an early stage after ICH synergisti...
Source: Journal of Neurochemistry - August 31, 2021 Category: Neuroscience Authors: Yang Yang, Xuezhu Chen, Zhizhong Feng, Xianfeng Cai, Xiaoming Zhu, Ming Cao, Likun Yang, Yujie Chen, Yuhai Wang, Hua Feng Tags: ORIGINAL ARTICLE Source Type: research

Preface: Cholinergic mechanisms
This special issue of the Journal of Neurochemistry, entitled ‘Cholinergic Mechanisms’, presents 15 reviews and 2 original papers, which have been selected so as to cover the broad range of topics and disciplines covered at the XVIth International Symposium on Cholinergic Mechanisms (ISCM-XVI). The authors discuss recent developments in the field, for inst ance, the association of cholinergic transmission with a number of important neurological and neuromuscular diseases in the central and peripheral nervous systems. AbstractThis special issue of theJournal of Neurochemistry, entitled “Cholinergic Mechani...
Source: Journal of Neurochemistry - August 30, 2021 Category: Neuroscience Authors: Lili Anglister, Israel Silman, Hermona Soreq Tags: EDITORIAL HIGHLIGHT Source Type: research

Spontaneous, transient adenosine release is not enhanced in the CA1 region of hippocampus during severe ischemia models
AbstractIschemic stroke causes damage in the brain and a slow buildup of adenosine is neuroprotective during ischemic injury. Spontaneous, transient adenosine signaling, lasting only 3 seconds per event, has been discovered that increases in frequency in the caudate-putamen during early stages of mild ischemia-reperfusion injury. However, spontaneous adenosine changes have not been studied in the hippocampus during ischemia, an area highly susceptible to stroke. Here, we investigated changes of spontaneous, transient adenosine in the CA1 region of rat hippocampus during three different models of varied intensity of ischemi...
Source: Journal of Neurochemistry - August 29, 2021 Category: Neuroscience Authors: Mallikarjunarao Ganesana, B. Jill Venton Tags: ORIGINAL ARTICLE Source Type: research

Issue Information
We present biochemical, proteomic, and electron microscopy evidence that support the influence of Tnik on Arc neurobiology by modifying its nuclear trafficking or oligomerization as virus-like capsids. These findings suggest new ways about how phosphorylation can shape the temporal and spatial regulation of Arc within neurons.Image content: Negative electron microscopy image shows bacterially expressed Arc protein forming virus-like double layered capsids.Read the full article ‘Phosphorylation-dependent control of Activity-regulated cytoskeleton-associated protein (Arc) protein by TNIK’ by A. Walczyk-Moora...
Source: Journal of Neurochemistry - August 26, 2021 Category: Neuroscience Tags: Issue Information Source Type: research

Association of serum Gasdermin D with Anti ‐N‐methyl‐D‐aspartate receptor encephalitis
In this study, we measured serum levels of GSDMD in 42 patients with anti-NMDAR encephalitis and 25 healthy controls. Of the 42 patients, 17 had follow-up evaluation of GSDMD levels and modified Rankin scale (mRS) scores at 3 months. Association of GSDMD with anti-NMDAR encephalitis and its clinical parameters were evaluated. Serum GSDMD levels were significantly higher in patients with anti-NMDAR encephalitis than in healthy controls (p = 0.002,padjusted = 0.009), especially in males (p = 0.001,padjusted = 0.022). This was also evident in patients with severe impairment (mRS>3 vs mRS ≤ 3;p
Source: Journal of Neurochemistry - August 21, 2021 Category: Neuroscience Authors: Xiaoyu Ma, Chen Chen, Yaxin Lu, Ling Fang, Baohua Cao, Xueqiang Hu, Wei Qiu, Yaqing Shu Tags: ORIGINAL ARTICLE Source Type: research

Protein profiling in the habenula after chronic ( –)‐menthol exposure in mice
In this report, we investigated the effects of chronic ( –)-menthol exposure in fourteen murine brain regions for changes in total β2 subunit protein levels and changes in epibatidine binding levels using immunoblotting and radioligand binding assays. We identified the habenula as a region of interest due to the region’s marked decreases in β2 subun it and nAChR levels in response to chronic (–)-menthol alone. Thus, we further examined the habenula, a brain region associated with both the reward and withdrawal components of addiction, for additional protein level alterations using mass spectrome...
Source: Journal of Neurochemistry - August 19, 2021 Category: Neuroscience Authors: Matthew J. Mulcahy, Stephanie M. Huard, Joao A. Paulo, Jonathan H. Wang, Sheri McKinney, Michael J. Marks, Brandon J. Henderson, Henry A. Lester Tags: ORIGINAL ARTICLE Source Type: research

MEC17 Induced α‐tubulin Acetylation Restores Mitochondrial Transport Function and Alleviates Axonal Injury after Intracerebral Hemorrhage in Mice
AbstractInjury to long axonal projections is a central pathological feature at the early phase of intracerebral hemorrhage (ICH). It has been reported to contribute to persistent functional disability following ICH. However, the molecular mechanisms that drive axonal degeneration remain unclear. Autologous blood was injected into the striatum to mimic the pathology of ICH. Observed significant swollen axons with characteristic retraction bulbs were found around the striatal hematoma at 24h after ICH. Electronic microscopic examination revealed highly disorganized microtubule and swollen mitochondria in the retraction bulbs...
Source: Journal of Neurochemistry - August 18, 2021 Category: Neuroscience Authors: Yang Yang, Xuezhu Chen, Zhizhong Feng, Xianfeng Cai, Xiaoming Zhu, Ming Cao, Likun Yang, Yujie Chen, Yuhai Wang, Hua Feng Tags: ORIGINAL ARTICLE Source Type: research

Issue Information
Front cover:Background: The C-terminal domain (CTD) of mGluR6 (residues 840-871) interacts with PDZ (postsynaptic density 95/discs large/zonula occludens-1)-containing scaffold proteins and G βγ subunits. We investigated whether CTD contributes to mGluR6 cell surface localization and receptor function. Immunocytochemical, biochemical, and electrophysiological approaches showed that deletions in the distal half of CTD attenuated mGluR6 surface localization and G-protein coupling, while further deletions comprising the distal two-thirds restored these functions. A sequence analysis revealed a putative ER retention...
Source: Journal of Neurochemistry - August 18, 2021 Category: Neuroscience Tags: Issue Information Source Type: research

A New Brain ‐Penetrant Glucosylceramide Synthase Inhibitor as Potential Therapeutics for Gaucher Disease
AbstractGaucher disease (GD), the most common lysosomal storage disorders, is caused byGBA gene mutations resulting in glycosphingolipids accumulations in various tissues, such as the brain. While suppressing glycosphingolipid accumulation is the central strategy for treating peripheral symptoms of GD, there is no effective treatment for the central nervous system symptoms. As glycosphingolipid biosynthesis starts from ceramide glycosylation by glucosylceramide synthase (GCS), inhibiting GCS in the brain is a promising strategy for neurological GD. Herein, we discovered T-036, a potent and brain-penetrant GCS inhibitor wit...
Source: Journal of Neurochemistry - August 16, 2021 Category: Neuroscience Authors: Takahiro Fujii, Yuta Tanaka, Hideyuki Oki, Sho Sato, Sachio Shibata, Takamitsu Maru, Yuta Tanaka, Maiko Tanaka, Tomohiro Onishi Tags: ORIGINAL ARTICLE Source Type: research

Sex and brain region ‐specific regulation of serotonin transporter activity in synaptosomes in guanine nucleotide‐binding protein G(q) alpha knockout mice
In this study, we show that the serotonin transporter (SERT) is sex specifically regulated by guanine nucleotide-binding protein alpha (G α)q. SERT-mediated uptake of 5-hydroxytryptamine (5HT) is enhanced in female Gαq knockout mice, which is correlated with differential Gαi1 expression in the midbrain, while in the frontal cortex the sexual dimorphism is caused by a down-regulation of SERT expression in male mice. The effects of G αq inhibitors, YM-254890 and BIM-46187, on SERT activity support the hypothesis that Gαq and Gαi, through direct interaction with SERT, inhibit 5HT uptake by ...
Source: Journal of Neurochemistry - August 13, 2021 Category: Neuroscience Authors: Jana Haase, Aim ée K. C. Jones, Conor J. Mc Veigh, Eric Brown, Gerard Clarke, Gudrun Ahnert‐Hilger Tags: ORIGINAL ARTICLE Source Type: research

Issue Information
Front cover:The expression of RAGE (receptor of advanced glycation end products) was increased on cerebral endothelial cells of mice after systemic infection of P. gingivalis (Porphyromonas gingivalis), a key pathogen of periodontal disease. The upregulated RAGE expressions on cerebral endothelial cells may involve in transporting peripheral A β into brain because RAGE is known as a receptor for peripheral Aβ influx.Image Content: Fluorescent image of brain slice stained with RAGE (green), CD31 (red) and Hoechst (blue) in mice after systemic P.gingivalis infection.Read the full article ‘Receptor for ad...
Source: Journal of Neurochemistry - August 12, 2021 Category: Neuroscience Tags: Issue Information Source Type: research

Receptor for advanced glycation end products up ‐regulation in cerebral endothelial cells mediates cerebrovascular‐related amyloid β accumulation after Porphyromonas gingivalis infection
In this 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 cultured hCMEC/D3 cell line, in comparison to uninfected cells, directly infection withP. gingivalis (multiplicity of infection, MOI  = 5) significantly increased a time-dependent RAGE expression resulting in a dramatic increase in Aβ influx in the hCMEC/D3 cells; theP. gingivalis-up-regulat...
Source: Journal of Neurochemistry - August 12, 2021 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