Glucocorticoids attenuate interleukin ‐6‐induced c‐Fos and Egr1 expression and impair neuritogenesis in PC12 cells
AbstractInterleukin ‐6 (IL‐6) is a cytokine primarily known for immune regulation. There is also growing evidence that IL‐6 triggers neurogenesis and impacts neural development, both life‐long occurring processes that can be impaired by early‐life and adult stress. Stress induces the release of glucocorticoid s by activation of the hypothalamic–pituitary–adrenal (HPA) axis. On the cellular level, glucocorticoids act via the ubiquitously expressed glucocorticoid receptor. Thus, we aimed to elucidate whether glucocorticoids affect IL‐6‐induced neural development. Here, we show that IL‐6 signallin ...
Source: Journal of Neurochemistry - January 17, 2021 Category: Neuroscience Authors: Hannes Bongartz, Elena Anne Sei ß, Jörg Bock, Fred Schaper Tags: ORIGINAL ARTICLE Source Type: research

Artemisinin inhibits TLR4 signaling by targeting co ‐receptor MD2 in microglial BV‐2 cells and prevents lipopolysaccharideinduced blood brain barrier leakage in mice
AbstractArtemisinin and its derivatives have been the frontline drugs for treating malaria. In addition to the antiparasitic effect, accumulating evidence shows that artemisinins can alleviate neuroinflammatory responses in the central nervous system (CNS). However, the precise mechanisms underlying their anti ‐neuroinflammatory effects are unclear. Herein we attempted to delineate the molecule target of artemisinin in microglia.In vitro protein intrinsic fluorescence titrations and saturation transfer difference (STD) ‐NMR showed the direct binding of artemisinin to TLR4 co‐receptor MD2. Cellular thermal shift assay...
Source: Journal of Neurochemistry - January 16, 2021 Category: Neuroscience Authors: Tianshu Zhang, Xiaozheng Zhang, Cong Lin, Siru Wu, Fanfan Wang, Hongshuang Wang, Yibo Wang, Yinghua Peng, Mark R. Hutchinson, Hongyuan Li, Xiaohui Wang Tags: ORIGINAL ARTICLE Source Type: research

The axonal endolysosomal and autophagic systems
The elaborate morphology and size of neurons, as well as their longevity, pose special challenges to autophagy and to the endolysosomal system, two of the main degradative routes for turnover of defective proteins and organelles. In this review, we discuss how axonal endosomes and autophagosomes form and select their cargo, how they are transported and mature along the axon and how they converge and join forces to mediate axonal signaling and recycling. AbstractNeurons, because of their elaborate morphology and the long distances between distal axons and the soma as well as their longevity, pose special challenges to autop...
Source: Journal of Neurochemistry - January 15, 2021 Category: Neuroscience Authors: Marijn Kuijpers, Domenico Azarnia Tehran, Volker Haucke, Tolga Soykan Tags: REVIEW Source Type: research

Dynamic subcellular localization and transcription activity of the SRF cofactor MKL2 in the striatum are regulated by MAPK
AbstractDopamine type 1 receptor (D1R) signaling activates protein kinase A (PKA), which then activates mitogen ‐activated protein kinase (MAPK) through Rap1, in striatal medium spiny neurons (MSNs). MAPK plays a pivotal role in reward‐related behavior through the activation of certain transcription factors. How D1R signaling regulates behavior through transcription factors remains largely unknown. CREB‐ binding protein (CBP) promotes transcription through hundreds of different transcription factors and is also important for reward‐related behavior. To identify transcription factors regulated by dopamine signaling ...
Source: Journal of Neurochemistry - January 15, 2021 Category: Neuroscience Authors: Anthony Ariza, Yasuhiro Funahashi, Sachi Kozawa, Md. Omar Faruk, Taku Nagai, Mutsuki Amano, Kozo Kaibuchi Tags: ORIGINAL ARTICLE Source Type: research

Phosphorylation of Collapsin Response Mediator Protein 1 (CRMP1) at Tyrosine 504 residue regulates Semaphorin 3A ‐induced cortical dendritic growth
AbstractCollapsin Response Mediator Proteins (CRMPs) have been identified as mediating proteins of repulsive axon guidance cue Semaphorin ‐3A (Sema3A). Phosphorylation of CRMPs plays a crucial role in the Sema3A signaling cascade. It has been shown that Fyn phosphorylates CRMP1 at Tyrosine 504 residue (Tyr504); however, the physiological role of this phosphorylation has not been examined. We found that CRMP1 was the most strongly ph osphorylated by Fyn among the five members of CRMPs. We confirmed Tyr504 phosphorylation of CRMP1 by Fyn. Immunocytochemistry of mouse dorsal root ganglion (DRG) neurons showed that phosphoty...
Source: Journal of Neurochemistry - January 15, 2021 Category: Neuroscience Authors: Takeshi Kawashima, Aoi Jitsuki ‐Takahashi, Kohtaro Takizawa, Susumu Jitsuki, Takuya Takahashi, Toshio Ohshima, Yoshio Goshima, Fumio Nakamura Tags: ORIGINAL ARTICLE Source Type: research

A balancing act: the role of pro ‐ and anti‐stress peptides within the central amygdala in anxiety and alcohol use disorders
AbstractThe central nucleus of the amygdala (CeA) is widely implicated as a structure that integrates both appetitive and aversive stimuli. While intrinsic CeA microcircuits primarily consist of GABAergic neurons that regulate amygdala output, a notable feature of the CeA is the heterogeneity of neuropeptides and neuropeptide/neuromodulator receptors that it expresses. There is growing interest in the role of the CeA in mediating psychopathologies, including stress and anxiety states and their interactions with alcohol use disorders. Within the CeA, neuropeptides and neuromodulators often exert pro ‐ or anti‐ stress ac...
Source: Journal of Neurochemistry - January 15, 2021 Category: Neuroscience Authors: Leigh C Walker Tags: REVIEW Source Type: research

MicroRNA ‐3473b regulates the expression of TREM2/ULK1 and inhibits autophagy in inflammatory pathogenesis of Parkinson’s disease
AbstractParkinson's disease (PD) is a neurodegenerative disease characterized by selective loss of dopaminergic(DA) neurons in the midbrain. The regulatory role of a variety of microRNAs in Parkinson's disease has been confirmed, and our study is the first to demonstrate that miR‐3473b is involved in the regulation o f Parkinson's disease. In vitro, an miR‐3473b inhibitor can inhibit the secretion of inflammatory factors (TNF‐α and IL‐1β) in moues microglia cell line(BV2) cells induced by lipopolysaccharide(LPS) and promote autophagy in BV2 cells. In vivo, miR‐3473b antagomir can inhibit the ac...
Source: Journal of Neurochemistry - January 15, 2021 Category: Neuroscience Authors: Qiankun Lv, Zhen Zhong, Binbin Hu, Si Yan, Yufang Yan, Junjun Zhang, Ting Shi, Lijuan Jiang, Wen Li, Wei Huang Tags: ORIGINAL ARTICLE Source Type: research

In vivo magnetic resonance spectroscopy in the brain of Cdkl5 null mice reveals a metabolic profile indicative of mitochondrial dysfunctions
In conclusion, MRS revealed in theCdkl5 null brain the presence of a metabolic dysregulation suggestive of a mitochondrial dysfunction that permitted to foster our comprehension ofCdkl5 deficiency and brought our interest towards targeting mitochondria as therapeutic strategy for CDD. (Source: Journal of Neurochemistry)
Source: Journal of Neurochemistry - January 15, 2021 Category: Neuroscience Authors: Sara Carli, Linda Chaabane, Clarissa Butti, Clara De Palma, Patrizia Aimar, Chiara Salio, Aglaia Vignoli, Maurizio Giustetto, Nicoletta Landsberger, Angelisa Frasca Tags: ORIGINAL ARTICLE Source Type: research

Using stable isotope labeling to advance our understanding of Alzheimer ’s disease etiology and pathology
AbstractStable isotope labeling with mass spectrometry (MS) ‐based proteomic analysis has become a powerful strategy to assess protein steady‐state levels, protein turnover, and protein localization. Applying these analyses platforms to neurodegenerative disorders may uncover new aspects of the etiology of these devastating diseases. Recently, stable iso topes‐MS has been used to investigate early pathological mechanisms of Alzheimer’s disease (AD) with mouse models of AD‐like pathology. In this review, we summarize these stable isotope‐MS experimental designs and the recent application in the context of AD...
Source: Journal of Neurochemistry - January 12, 2021 Category: Neuroscience Authors: Timothy J. Hark, Jeffrey N. Savas Tags: REVIEW Source Type: research

Crystal structure of glutamate dehydrogenase 2, a positively selected novel human enzyme involved in brain biology and cancer pathophysiology
ConclusionsOur data provide insights into the structural basis of hGDH2 properties, the functional evolution of hGDH isoenzymes, and open new prospects for drug design, especially for cancer therapeutics. (Source: Journal of Neurochemistry)
Source: Journal of Neurochemistry - January 9, 2021 Category: Neuroscience Authors: Christina Dimovasili, Vasiliki E. Fadouloglou, Aikaterini Kefala, Mary Providaki, Dina Kotsifaki, Konstantinos Kanavouras, Iosifina Sarrou, Andreas Plaitakis, Ioannis Zaganas, Michael Kokkinidis Tags: ORIGINAL ARTICLE Source Type: research

Late post ‐natal neurometabolic development in healthy male rats using 1H and 31P Magnetic Resonance Spectroscopy
In conclusion, the present study showed important changes in brain metabolites in both the hippocampus and cerebellum in the later post ‐natal period (p29/p35‐p77) of male rats, something previously unreported. Based on these novel data, changes in some neurometabolites beyond p28‐35, conventionally accepted as the cut off for adulthood, should be taken into account in both experimental design and data interpretation in this a nimal model. (Source: Journal of Neurochemistry)
Source: Journal of Neurochemistry - January 9, 2021 Category: Neuroscience Authors: Veronika Ra čkayová, Dunja Simicic, Guillaume Donati, Olivier Braissant, Rolf Gruetter, Valérie A. McLin, Cristina Cudalbu Tags: ORIGINAL ARTICLE Source Type: research

Proteomics and metabolomics of HIV ‐associated neurocognitive disorders: a systematic review
AbstractHIV ‐associated neurocognitive disorders (HAND) are common features of the effect of human immunodeficiency virus (HIV)‐1 within the central nervous system (CNS). The underlying neuropathophysiology of HAND is incompletely known. Further, there are no markers to effectively predict or stratify the r isk of HAND. Recent advancements in the fields of proteomics and metabolomics have shown promise in addressing these concerns, however, it is not clear if these approaches may provide new insight into pathways and markers related to HAND. We therefore conducted a systematic review of studies using p roteomic and/or ...
Source: Journal of Neurochemistry - January 9, 2021 Category: Neuroscience Authors: Monray E. Williams, Petrus J.W. Naud é, Francois H. van der Westhuizen Tags: REVIEW Source Type: research

Circuit Selectivity in Drug Versus Natural Reward Seeking Behaviors
AbstractSubstance use disorder (SUD) is characterized, in part by behavior biased toward drug use and away from natural sources of reward (e.g. social interaction, food, sex). The neurobiological underpinnings of SUDs reveal distinct brain regions where neuronal activity is necessary for the manifestation of SUD ‐characteristic behaviors. Studies that specifically examine how these regions are involved in behaviors motivated by drug versus natural reward allow determinations of which regions are necessary for regulating seeking of both reward types, and appraisals of novel SUD therapies for off‐target e ffects on behav...
Source: Journal of Neurochemistry - January 8, 2021 Category: Neuroscience Authors: Rusty W. Nall, Jasper A. Heinsbroek, Todd B. Nentwig, Peter W. Kalivas, Ana ‐Clara Bobadilla Tags: REVIEW Source Type: research

The multi ‐functional RNA‐binding protein G3BP1 and its potential implication in neurodegenerative disease
G3BP1 (Ras ‐GTPase‐activating protein (GAP)‐binding protein 1) is a multi‐functional protein involved in the assembly and dynamics of stress granules, and also other functions related to RNA metabolism. G3BP1 has been therapeutically targeted in cancers as its over‐expression is correlated with the p roliferation of cancerous cells and metastasis. However, evidence suggests that G3BP1 is essential for neuronal development and possibly neuronal maintenance. The current Review examines the various functions of G3BP1 in the context of neurons, and we speculate how these functions are critical to th e progression of ...
Source: Journal of Neurochemistry - January 8, 2021 Category: Neuroscience Authors: Hadjara Sidib é, Alicia Dubinski, Christine Vande Velde Tags: REVIEW Source Type: research

Heterogeneity of microglial proton channel in different brain regions and its relationship with aging
AbstractThe properties of microglia largely differ depending on aging as well as on brain regions. However, there are few studies that investigated the functional importance of such heterogeneous properties of microglia at molecular level. Voltage ‐gated proton channel, Hv1/VSOP, could be one of the candidates which confers functional heterogeneity among microglia, since it regulates brain oxidative stress in age‐dependent manner. In the present study, we found that Hv1/VSOP shows brain region‐dependent heterogeneity of gene expression with highest level in striatum. We studied the importance of Hv1/VSOP in two diffe...
Source: Journal of Neurochemistry - January 6, 2021 Category: Neuroscience Authors: Takafumi Kawai, Keizo Takao, Sharmin Akter, Manabu Abe, Kenji Sakimura, Tsuyoshi Miyakawa, Yasushi Okamura Tags: ORIGINAL ARTICLE Source Type: research

Rho ‐kinase inhibition by fasudil modulates pre‐synaptic vesicle dynamics
Chronic treatment with the Rho kinase (ROCK) inhibitor fasudil did not affect basic synaptic protein abundance, but altered synaptic vesicles dynamics. In stimulated cultures, fasudil reduced synapsin1 phosphorylation and the size of the recycling pool. We propose that over ‐active vesicles thus are degraded faster reducing the synaptic response upon stimulation. This broadens the spectrum of fasudil effects suggesting new clinical uses of this drug. AbstractThe Rho kinase (ROCK) signaling pathway is an attractive therapeutic target in neurodegeneration  since it has been linked to the prevention of neuronal de...
Source: Journal of Neurochemistry - January 6, 2021 Category: Neuroscience Authors: Kim Ann Saal, Carmina Warth P érez Arias, Anna‐Elisa Roser, Jan Christoph Koch, Mathias Bähr, Silvio O. Rizzoli, Paul Lingor Tags: ORIGINAL ARTICLE Source Type: research

Collybistin SH3 ‐protein isoforms are expressed in the rat brain promoting gephyrin and GABA‐A receptor clustering at GABAergic synapses
ARHGEF9 encodes several collybistin splice variants which can be grouped into ones that possess the auto ‐inhibitory SH3 domain (CBSH3+) and ones that do not (CBSH3−), the latter being constitutively active. CBSH3+ and CBSH3− bind to gephyrin forming the GABAergic postsynaptic scaffold. The predominant CBSH3+ isoform has been extensively studied but not CBSH3−, whose function has been largely o verlooked. We are now showing that CBSH3− variants play a significant role in regulating the size of the postsynaptic GABAergic scaffold. AbstractCollybistin (CB) is a guanine nucleotide exchange factor (GE...
Source: Journal of Neurochemistry - January 5, 2021 Category: Neuroscience Authors: Shanu George, John Bear, Michael J. Taylor, Karthik Kanamalla, Christopher D. Fekete, Tzu ‐Ting Chiou, Celia P. Miralles, Theofilos Papadopoulos, Angel L. De Blas Tags: ORIGINAL ARTICLE Source Type: research

Ten years of editing the Journal of Neurochemistry
Journal of Neurochemistry, EarlyView. (Source: Journal of Neurochemistry)
Source: Journal of Neurochemistry - January 2, 2021 Category: Neuroscience Tags: NEWS & ISN Source Type: research

Cyclooxygenase inhibition attenuates brain angiogenesis and independently decreases mouse survival under hypoxia
AbstractAlthough cyclooxygenase (COX) role in cancer angiogenesis has been studied, little is known about its role in brain angioplasticity. In the present study, we chronically infused mice with ketorolac, a non ‐specific COX inhibitor that does not cross the blood‐brain barrier (BBB), under normoxia or 50% isobaric hypoxia (10% O2 by volume). Ketorolac increased mortality rate under hypoxia in a dose ‐dependent manner. Usingin vivo multiphoton microscopy, we demonstrated that chronic COX inhibition completely attenuated brain angiogenic response to hypoxia. Alterations in a number of angiogenic factors that were re...
Source: Journal of Neurochemistry - January 2, 2021 Category: Neuroscience Authors: Drew R. Seeger, Svetlana A. Golovko, Bryon D. Grove, Mikhail Y. Golovko Tags: ORIGINAL ARTICLE Source Type: research

Bile ‐duct ligation renders the brain susceptible to hypotension induced neuronal degeneration: implications of ammonia
AbstractHepatic encephalopathy (HE) is a debilitating neurological complication of cirrhosis. By definition, HE is considered a reversible disorder, and therefore HE should resolve following liver transplantation (LT). However, persisting neurological complications are observed in as many as 47% of LT recipients. LT is an invasive surgical procedure accompanied with various perioperative factors such as blood loss and hypotension which could influence outcomes post ‐LT. We hypothesize that minimal HE (MHE) renders the brain frail and susceptible to hypotension‐induced neuronal cell death. Six‐week bile duct‐ligated...
Source: Journal of Neurochemistry - December 31, 2020 Category: Neuroscience Authors: Marc ‐André Clément, Cristina R. Bosoi, Mariana M. Oliveira, Mélanie Tremblay, Chantal Bémeur, Christopher F. Rose Tags: ORIGINAL ARTICLE Source Type: research

Neuromuscular Junction ‐on‐a‐Chip: ALS disease modeling and read‐out development in microfluidic devices
We describe and discuss the relevance of these read‐outs and specifically illustrate how these read‐outs have enhanced our understanding of NMJ pathology in ALS. Finally, we share our view on potential future directions and challenges. (Source: Journal of Neurochemistry)
Source: Journal of Neurochemistry - December 31, 2020 Category: Neuroscience Authors: Rianne de Jongh, Xandor M. Spijkers, Svetlana Pasteuning ‐Vuhman, Paul Vulto, R. Jeroen Pasterkamp Tags: REVIEW Source Type: research

Exosomes in Parkinson Disease
AbstractParkinson disease (PD) is a prevalent neurodegenerative disease, in which the formation of misfolded and aggregated α‐synuclein is a key neuropathological hallmark. Recent studies reveal that extracellular vesicles such as exosomes present a potential mechanism for propagation of pathological α‐synuclein throughout the brain. The ability of exosomes to transport proteins and genetic material between cells, including mRNA and microRNAs which have been implicated in PD pathology, provides critical insights as to how exosomes may contribute to pathological progression in PD. Advances have also been mad...
Source: Journal of Neurochemistry - December 29, 2020 Category: Neuroscience Authors: Jennifer R. Pinnell, Mei Cui, Kim Tieu Tags: REVIEW Source Type: research

A multi ‐level assessment of the bidirectional relationship between aging and the circadian clock
AbstractThe daily temporal order of physiological processes and behavior contribute to the wellbeing of many organisms including humans. The central circadian clock, which coordinates the timing within our body, is located in the suprachiasmatic nucleus (SCN) of the hypothalamus. Like other parts of the brain, aging impairs the SCN function, which in turn promotes the development and progress of aging related diseases. We here review the impact of aging on the different levels of the circadian clock machinery ‐ from molecules to organs – with a focus on the role of the SCN. We find that the molecular clock is less ...
Source: Journal of Neurochemistry - December 28, 2020 Category: Neuroscience Authors: M.Renate Buijink, Stephan Michel Tags: REVIEW Source Type: research

The axonal endo ‐lysosomal and autophagic systems
AbstractNeurons, because of their elaborate morphology and the long distances between distal axons and the soma as well as their longevity, pose special challenges to autophagy and to the endolysosomal system, two of the main degradative routes for turnover of defective proteins and organelles. Autophagosomes sequester cytoplasmic or organellar cargos by engulfing them into their lumen before fusion with degradative lysosomes enriched in neuronal somata and participate in retrograde signaling to the soma. Endosomes are mainly involved in the sorting, recycling, or lysosomal turnover of internalized or membrane ‐bound mac...
Source: Journal of Neurochemistry - December 28, 2020 Category: Neuroscience Authors: Marijn Kuijpers, Domenico Azarnia Tehran, Volker Haucke, Tolga Soykan Tags: REVIEW Source Type: research

fISHing with immunohistochemistry for housekeeping gene changes in Alzheimer ’s disease using an automated quantitative analysis workflow
AbstractIn situ hybridization (ISH) is a powerful tool that can be used to localize mRNA expression in tissue samples. Combining ISH with immunohistochemistry (IHC) to determine cell type provides cellular context of mRNA expression, which cannot be achieved with gene microarray or polymerase chain reaction. To study mRNA and protein expression on the same section we investigated the use of RNAscope ® ISH in combination with fluorescent IHC on paraffin‐embedded human brain tissue. First, we developed a high‐throughput, automated image analysis workflow for quantifying RNA puncta across the total cell population and...
Source: Journal of Neurochemistry - December 25, 2020 Category: Neuroscience Authors: Blake Highet, Praju Vikas Anekal, Brigid Ryan, Helen Murray, Natacha Coppieters, Birger Victor Dieriks, Malvindar K. Singh ‐Bains, Nasim F. Mehrabi, Richard L.M. Faull, Michael Dragunow, Maurice A. Curtis Tags: ORIGINAL ARTICLE Source Type: research

An altered secretome is an early marker of the pathogenesis of CLN6 Batten disease
This study investigated th e secretome in the CLN6 (ceroid‐lipofuscinosis neuronal protein 6) variant of NCL. To investigate the CLN6 secretome, we co‐cultured neurons and glia isolated fromCln6nclf or Cln6+/ ‐ mice, and utilised mass spectrometry to compare protein constituents of conditioned media. The significant changes noted in cathepsin enzymes, were investigated further via western blotting and enzyme activity assays. Viral ‐mediated gene therapy was used to try and rescue the wild‐type phenotype and restore the secretome – bothin vitro in co ‐cultures andin vivo in mouse plasma. InCln6nclf cells, ...
Source: Journal of Neurochemistry - December 25, 2020 Category: Neuroscience Authors: Hannah L. Best, Alison J. Clare, Kirstin O. McDonald, Hollie E. Wicky, Stephanie M. Hughes Tags: ORIGINAL ARTICLE Source Type: research

Microbiota ‐Gut‐Brain Axis as a Regulator of Reward Processes
AbstractOur gut harbours trillions of microorganisms essential for the maintenance of homeostasis and host physiology in health and disease. In the last decade, there has been a growing interest in understanding the bidirectional pathway of communication between our microbiota and the central nervous system. With regard to reward processes there is accumulating evidence from both animal and human studies that this axis may be a key factor in gating reward valence. Focusing on the mesocorticolimbic pathway, we will discuss how the intestinal microbiota is involved in regulating brain reward functions, both in natural (i.e.,...
Source: Journal of Neurochemistry - December 25, 2020 Category: Neuroscience Authors: Rub én García‐Cabrerizo, Carina Carbia, Kenneth J. O´Riordan, Harriet Schellekens, John F. Cryan Tags: REVIEW Source Type: research

Cytisine is neuroprotective in female but not male 6 ‐hydroxydopamine lesioned parkinsonian mice and acts in combination with 17‐β‐estradiol to inhibit apoptotic endoplasmic reticulum stress in dopaminergic neurons
AbstractApoptotic endoplasmic reticulum (ER) stress is a major mechanism for dopaminergic (DA) loss in Parkinson ’s disease (PD). We assessed if low doses of the partial α4β2 nicotinic acetylcholine receptor (nAChR) agonist, cytisine attenuates apoptotic ER stress and exerts neuroprotection in substantia nigra pars compacta (SNc) DA neurons. Alternate day intraperitoneal injections of 0.2 mg/kg cytisine we re administered to female and male mice with 6‐hydroxydopamine (6‐OHDA) lesions in the dorsolateral striatum, which caused unilateral degeneration of SNc DA neurons. Cytisine attenuated 6‐OHDA‐in...
Source: Journal of Neurochemistry - December 23, 2020 Category: Neuroscience Authors: Sara M. Zarate, Gauri Pandey, Sunanda Chilukuri, Jose A. Garcia, Brittany Cude, Shannon Storey, Nihal A. Salem, Eric A. Bancroft, Michelle Hook, Rahul Srinivasan Tags: ORIGINAL ARTICLE Source Type: research

FUS regulates autophagy by mediating the transcription of genes critical to the autophagosome formation
AbstractFused in Sarcoma (FUS) is a ubiquitously expressed RNA/DNA ‐binding protein that plays different roles in the cell. FUS pathology has been reported in neurodegenerative diseases amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Mutations in FUS have also been linked to a subset of familial ALS. FUS is mainly localized in the nucleus a lthough it shuttles between the nucleus and the cytoplasm. ALS‐linked mutations cause the accumulation of the FUS protein in cytoplasm where it forms stress granule‐like inclusions. The protein‐ and RNA‐containing inclusions are reported to be positive o...
Source: Journal of Neurochemistry - December 22, 2020 Category: Neuroscience Authors: Alexandra Arenas, Lisha Kuang, Jiayu Zhang, Meagan S. Kingren, Haining Zhu Tags: ORIGINAL ARTICLE Source Type: research

The multi ‐functional RNA binding protein G3BP1 and its potential implication in neurodegenerative disease
AbstractG3BP1 is a multi ‐functional protein that is best known for its role in the assembly and dynamics of stress granules. Recent studies have highlighted that G3BP1 also has other functions related to RNA metabolism. In the context of disease, G3BP1 has been therapeutically targeted in cancers because its overexpressi on is correlated with proliferation of cancerous cells and metastasis. However, evidence suggests that G3BP1 is essential for neuronal development and possibly neuronal maintenance. In this review, we will examine the many functions that are carried out by G3BP1 in the context of neurons and specula te ...
Source: Journal of Neurochemistry - December 22, 2020 Category: Neuroscience Authors: Hadjara Sidib é, Alicia Dubinski, Christine Vande Velde Tags: REVIEW Source Type: research

Hyaluronidase inhibition accelerates functional recovery from stroke in the mouse brain
AbstractPerineuronal nets (PNNs) are presumed to limit plasticity in adult animals. Ischemic stroke results in the massive breakdown of PNNs resulting in rejuvenating states of neuronal plasticity, but the mechanisms of this phenomenon are largely unknown. As hyaluronic acid (HA) is the structural backbone of PNNs, we hypothesized that these changes are a consequence of altered expression of HA metabolism enzymes. Additionally, we investigated whether early hyaluronidase inhibition interferes with poststroke PNN reduction and behavioural recovery.We investigated the mRNA/protein expression of these enzymes in the perilesio...
Source: Journal of Neurochemistry - December 20, 2020 Category: Neuroscience Authors: Anna Katarzyna Greda, Dorota Nowicka Tags: ORIGINAL ARTICLE Source Type: research

Rho ‐Kinase Inhibition by Fasudil Modulates Presynaptic Vesicle Dynamics
AbstractThe Rho kinase (ROCK) signaling pathway is an attractive therapeutic target in neurodegeneration  since it has been linked to the prevention of neuronal death and neurite regeneration. The isoquinoline derivative fasudil is a potent ROCK inhibitor, which is already approved for chronic clinical treatment in humans. However, the effects of chronic fasudil treatments on neuronal function a re still unknown. We analyzed here chronic fasudil treatment in primary rat hippocampal cultures. Neurons were stimulated with 20 Hz field stimulation and we investigated presynaptic mec...
Source: Journal of Neurochemistry - December 20, 2020 Category: Neuroscience Authors: Kim Ann Saal, Carmina Warth P érez Arias, Anna‐Elisa Roser, Jan Christoph Koch, Mathias Bähr, Silvio O. Rizzoli, Paul Lingor Tags: ORIGINAL ARTICLE Source Type: research

Aminoacyl ‐tRNA synthetases in Charcot–Marie–Tooth disease: A gain or a loss?
Variants of some aminoacyl ‐tRNA synthetases (aaRS) are strongly associated with Charcot–Marie–Tooth disease (CMT), one of the most common inherited neuromuscular disorders. Some variants affect enzymatic activity, showing loss‐of‐function effects. In contrast, evidence from CMT patient samples, animal genetic studi es or protein conformational analysis has confirmed toxic gain‐of‐function of some aaRSs variants in CMT outside of aminoacylation. In this review, we will discuss the latest advances in studies on CMT‐associated aaRSs, with a particular focus on the complicated mechanisms in the pathoge...
Source: Journal of Neurochemistry - December 19, 2020 Category: Neuroscience Authors: Han Zhang, Zhong ‐Wei Zhou, Litao Sun Tags: Review Source Type: research

Activation of Wnt/ β‐catenin signaling restores insulin sensitivity in insulin resistant neurons through transcriptional regulation of IRS‐1
In this study, we aimed to investigate the regulation of IRS‐1 and its downstream insulin signaling by Wnt/β‐catenin signaling in primary neurons. We found that the Wnt agonist Wnt3a enhances the insulin signaling in neurons at the basal state via upregulation of IRS‐1. Moreover, Wnt3a up regulates IRS‐1 expression and effectively ameliorates insulin resistance in rat primary neurons induced by chronic high insulin exposure. The insulin mediated glucose uptake is also stimulated by Wnt3a at both basal and insulin resistant states. We observed that Wnt activation upregulates IRS‐1 gene transcription and the s...
Source: Journal of Neurochemistry - December 18, 2020 Category: Neuroscience Authors: Shijiao Tian, Shichuan Tan, Wenming Jia, Juan Zhao, Xiulian Sun Tags: ORIGINAL ARTICLE Source Type: research

Alpha ‐Synuclein oligomerization and aggregation: All models are useful but only if we know what they model
AbstractAlpha ‐synuclein oligomerization is one of the early events on the pathway to Lewy body formation. Therefore, interfering with this process holds tremendous potential for developing therapies that block α‐Syn pathology formation and toxicity. The development of robust and reliable cellular models of alpha‐synuclein oligomerization is one important step towards achieving this goal. Unlike α‐Syn fibrils, which can be detected and labeled using multiple tools and validated antibodies, α‐Syn oligomers are very difficult to differentiate from soluble monomeric α‐Syn in cells. This has...
Source: Journal of Neurochemistry - December 18, 2020 Category: Neuroscience Authors: Hilal A. Lashuel Tags: LETTER TO THE EDITOR Source Type: research

Rapid Vesicle Replenishment after the Immediately Releasable Pool Exocytosis is tightly linked to Fast Endocytosis, and depends on Basal Calcium and Cortical Actin in Chromaffin Cells
AbstractThe maintenance of the secretory response requires a continuous replenishment of releasable vesicles. It was proposed that the immediately releasable pool (IRP) is important in chromaffin cell secretion during action potentials applied at basal physiological frequencies, because of the proximity of IRP vesicles to voltage dependent Ca2+ channels. However, previous reports showed that IRP replenishment after depletion is too slow to manage such a situation. In this work we used patch ‐clamp measurements of membrane capacitance, confocal imaging of F‐actin distribution and cytosolic Ca2+ measurements with Fura ...
Source: Journal of Neurochemistry - December 18, 2020 Category: Neuroscience Authors: Mauricio Montenegro, Lucas Bayon és, José Moya‐Díaz, Cecilia Borassi, Andrés Martín Toscani, Luciana I. Gallo, Fernando D. Marengo Tags: ORIGINAL ARTICLE Source Type: research

The lipid phosphatase ‐like protein PLPPR1 associates with RhoGDI1 to modulate RhoA activation in response to axon growth inhibitory molecules
AbstractPhospholipid Phosphatase ‐Related Protein Type 1 (PLPPR1) is a member of a family of lipid phosphatase related proteins, integral membrane proteins characterized by six transmembrane domains. This family of proteins is enriched in the brain and recent data indicate potential pleiotropic functions in several different cont exts. An inherent ability of this family of proteins is to induce morphological changes, and we have previously reported that members of this family interact with each other and may function co‐operatively. However, the function of PLPPR1 is not yet understood. Here we show that expression of ...
Source: Journal of Neurochemistry - December 15, 2020 Category: Neuroscience Authors: Chinyere Agbaegbu Iweka, Rowan K. Hussein, Panpan Yu, Yasuhiro Katagiri, Herbert M Geller Tags: ORIGINAL ARTICLE Source Type: research

Phosphatidylinositol ‐3 kinase mediates the sweet suppressive effect of leptin in mouse taste cells
AbstractLeptin is known to selectively suppress neural and taste cell responses to sweet compounds. The sweet suppressive effect of leptin is mediated by the leptin receptor Ob ‐Rb, and the ATP‐gated K+ (KATP) channel expressed in some sweet ‐sensitive, T1R3‐positive taste cells. However, the intracellular transduction pathway connecting Ob‐Rb to KATP channel remains unknown. Here we report that phosphoinositide 3 ‐kinase (PI3K) mediates leptin’s suppression of sweet responses in T1R3‐positive taste cells. Inin situ taste cell recording, systemically administrated leptin suppressed taste cell responses ...
Source: Journal of Neurochemistry - December 15, 2020 Category: Neuroscience Authors: Ryusuke Yoshida, Robert F. Margolskee, Yuzo Ninomiya Tags: ORIGINAL ARTICLE Source Type: research

Collybistin SH3 ‐ protein isoforms are expressed in the rat brain promoting gephyrin and GABA‐A receptor clustering at GABAergic synapses
AbstractCollybistin (CB) is a guanine nucleotide exchange factor (GEF) selectively localized at GABAergic and glycinergic postsynapses. Analysis of mRNA shows that several isoforms of collybistin are expressed in the brain. Some of the isoforms have a SH3 domain (CBSH3+) and some have no SH3 domain (CBSH3 ‐). The CBSH3+ mRNAs are predominantly expressed over CBSH3‐. However, in an immunoblot study of mouse brain homogenates, only CBSH3+ protein isoforms were detected, proposing that CBSH3‐ protein might not be expressed in the brain. The expression or lack of expression of CBSH3‐ protein is a n important issue beca...
Source: Journal of Neurochemistry - December 14, 2020 Category: Neuroscience Authors: Shanu George, John Bear, Michael J. Taylor, Karthik Kanamalla, Christopher D. Fekete, Tzu ‐Ting Chiou, Celia P. Miralles, Theofilos Papadopoulos, Angel L. De Blas Tags: ORIGINAL ARTICLE Source Type: research

Neuroprotection offered by mesenchymal stem cells in perinatal brain injury: Role of mitochondria, inflammation and reactive oxygen species
AbstractPreclinical studies have shown that mesenchymal stem cell have a positive effect in perinatal brain injury models. The mechanisms that cause these neurotherapeutic effects are not entirely intelligible. Mitochondrial damage, inflammation and reactive oxygen species are considered to be critically involved in the development of injury. Mesenchymal stem cells have immunomodulatory action and exert mitoprotective effects which attenuate production of reactive oxygen species and promote restoration of tissue function and metabolism after perinatal insults. This review summarizes the present state, the underlying causes...
Source: Journal of Neurochemistry - December 12, 2020 Category: Neuroscience Authors: Syam Nair, Eridan Rocha ‐Ferreira, Bobbi Fleiss, Cora H Nijboer, Pierre Gressens, Carina Mallard, Henrik Hagberg Tags: REVIEW Source Type: research

The Dialog between Neurons and Microglia in Alzheimer's Disease: The Neurotransmitters View
AbstractMicroglia play a vital role in maintaining brain homeostasis. Their continuous sensing of surrounding micro ‐environments is crucial for their activity. Cross talk between specific neurons and microglia might occur through specific neurotransmitter receptors on microglia. Impairment with this interaction might result in pathological activity of microglia against potential insults. The reason for this ac tivity in many neurodegenerative diseases such as Alzheimer's disease (AD) is not known. However, several papers report of the effects of different neurotransmitter agonists on microglial cells function that relat...
Source: Journal of Neurochemistry - December 12, 2020 Category: Neuroscience Authors: Nofar Stolero, Dan Frenkel Tags: REVIEW Source Type: research

Glucocorticoid ‐mediated mechanisms of hippocampal damage: contribution of subgranular neurogenesis
AbstractA  comprehensive overview of the interplay between glucocorticoids (GCs) and adult hippocampal neurogenesis (AHN) is presented, particularly, in the context of a diseased brain. The effectors of GCs in the dentate gyrus neurogenic niche of the hippocampal are reviewed, and the consequences of the G C signaling on the generation and integration of new neurons are discussed. Recent findings demonstrating how GC signaling mediates impairments of the AHN in various brain pathologies are overviewed. GC‐mediated effects on the generation and integration of adult‐born neurons in the hippocampal d entate...
Source: Journal of Neurochemistry - December 10, 2020 Category: Neuroscience Authors: Oleg V. Podgorny, Natalia V. Gulyaeva Tags: REVIEW Source Type: research

Cortical VIP+/ChAT+ interneurons: from genetics to function
AbstractOne of the urgent tasks of neuroscience is to understand how neuronal circuits operate, what makes them fail, and how to repair them when needed. Achieving this goal requires identifying the principal circuitry elements and their interactions with one another. However, what constitutes “an atom” of a neuronal circuit, a neuronal type, is a complex question. In this review we focus on a class of cortical neurons that are exclusively identified by the expression of vasoactive intestinal polypeptide (VIP) and choline acetyltransferase (ChAT). The genetic profile of these VIP+/ChAT+ interneurons suggests th...
Source: Journal of Neurochemistry - December 10, 2020 Category: Neuroscience Authors: Amir Dudai, Nadav Yayon, Hermona Soreq, Michael London Tags: REVIEW Source Type: research

Nicotinamide ameliorates energy deficiency and improves retinal function in Cav ‐1‐/‐ mice
In this study, NAM was administrated orally for two weeks in Cav‐1‐/‐ mice before experiments. Oxidative lipidomics was conducted to detect the oxylipin changes, the retinal energy flux was measured by seahorse assay, and the retinal function was assessed by electroretinogram (ERG). Cav ‐1 deficiency induced dysregulation of oxidative lipidomics and reduction in energy consumption/production in the retina by decreasing Na+/K+‐ATPase, oxidative phosphorylation CII, cytochrome c and oxygen consumption rate(OCR). A decrease in Sirt1 was also detected. Therapeutic administration of NAM significantly increased Sirt1 e...
Source: Journal of Neurochemistry - December 10, 2020 Category: Neuroscience Authors: Yizhen Tang, Wangyi Fang, Zebin Xiao, Maomao Song, Dongli Zhuang, Binze Han, Jihong Wu, Xinghuai Sun Tags: ORIGINAL ARTICLE Source Type: research

Acknowledgement of Reviewers
Journal of Neurochemistry, Volume 155, Issue 6, Page 714-715, December 2020. (Source: Journal of Neurochemistry)
Source: Journal of Neurochemistry - December 9, 2020 Category: Neuroscience Tags: ACKNOWLEDGEMENT OF REVIEWERS Source Type: research

Issue Cover (December 2020)
Front cover:Amyloid ‐beta (Aβ) is recognized as a danger‐associated molecular pattern by pattern recognition receptors present on microglial cells. The aim of the study was to analyze whether low molecular weight Aβ oligomers, which are stronger neurotoxic than fibrils, could activate NLRP3 inflammasome in microg lial cells. This activation was confirmed using nigericin, a well‐known NLRP3 stimulus. Inflammasome activation is represented by caspase‐1 activation and IL‐1β release. Our results confirm that NLRP3 inflammasome is activated not only by fibrils forming Aβ aggregates but also by smal...
Source: Journal of Neurochemistry - December 9, 2020 Category: Neuroscience Tags: Issue Cover Source Type: research

Issue Information
Journal of Neurochemistry, Volume 155, Issue 6, Page 593-598, December 2020. (Source: Journal of Neurochemistry)
Source: Journal of Neurochemistry - December 9, 2020 Category: Neuroscience Tags: Issue Information Source Type: research

Alpha ‐synuclein oligomerization and aggregation: a model will always be a model
AbstractMany different types of protein aggregates have attracted the minds and curiosity of countlessarmies of scientists, i.e., laboratories, in the world for more than 100 years. For example, it was in 1912 that F. Lewy reported the presence of structures, eternalized as Lewy bodies (LBs) and Lewy neurites (LNs), in the brains of patients with Parkinson ’s disease (Lewy 1912). Since then, tremendous efforts have been dedicated to figuring out how such deposits ‘cause’ Parkinson’s disease. In 1997, with the identification of alpha‐synuclein (aSyn) as the major protein component of LBs and LNs (S...
Source: Journal of Neurochemistry - December 9, 2020 Category: Neuroscience Authors: Tiago Fleming Outeiro Tags: LETTER TO THE EDITOR Source Type: research

New perspective on the regulation of acetylcholinesterase via the aryl hydrocarbon receptor
AbstractAcetylcholinesterase (AChE, EC 3.1.1.7) plays important roles in cholinergic neurotransmission and has been widely recognized as a biomarker for monitoring pollution by organophosphate (OP) and carbamate pesticides. Dioxin is an emerging environmental AChE disruptor and is a typical persistent organic pollutant with multiple toxic effects on the nervous system. Growing evidence has shown that there is a significant link between dioxin exposure and neurodegenerative diseases and neurodevelopmental disorders, most of which involve AChE and cholinergic dysfunctions. Therefore, an in ‐depth understanding of the effec...
Source: Journal of Neurochemistry - December 5, 2020 Category: Neuroscience Authors: Heidi Qunhui Xie, Yongchao Ma, Hualing Fu, Tuan Xu, Yali Luo, Yiyun Liu, Yangsheng Chen, Li Xu, Yingjie Xia, Bin Zhao Tags: REVIEW Source Type: research

Pimavanserin, a 5HT2A receptor inverse agonist, rapidly suppresses A β production and related pathology in a mouse model of Alzheimer’s disease
AbstractAmyloid ‐β (Aβ) peptide aggregation into soluble oligomers and insoluble plaques is a precipitating event in the pathogenesis of Alzheimer’s disease (AD). Given that synaptic activity can regulate Aβ generation, we postulated that 5HT2A‐Rs may regulate Aβ as well. We treated APP/PS1 transgenic mice with the selective 5HT2A inverse agonists M100907 or Pimavanserin systemically and measured brain interstitial fluid (ISF) A β levels in real‐time using in vivo microdialysis. Both compounds reduced ISF Aβ levels by almost 50% within hours, but had no effect on Aβ levels in ...
Source: Journal of Neurochemistry - December 5, 2020 Category: Neuroscience Authors: Carla M. Yuede, Clare E. Wallace, Todd A. Davis, Woodrow D. Gardiner, Jane C. Hettinger, Hannah M. Edwards, Rachel D. Hendrix, Brookelyn M. Doherty, Kayla M. Yuede, Ethan S. Burstein, John R. Cirrito Tags: ORIGINAL ARTICLE Source Type: research