Acetylcholine release from striatal cholinergic interneurons is controlled differently depending on the firing pattern
How is the quantal size in neurotransmitter release adjusted for various firing levels?We proposed three distinct processes of acetylcholine (ACh) release from releasable pool of striatal cholinergic interneurons; (A) selective release of rapid releasable ACh upon short stimulation, (B) release of rapid releasable and replenished ACh during long stimulation, and (C) missing release upon high-frequency stimulation. The fine tuning of ACh release may play an important physiological role in self-protection against excessive excitation/discharge in cholinergic interneurons. AbstractHow is the quantal size in neurotransmitter r...
Source: Journal of Neurochemistry - September 1, 2023 Category: Neuroscience Authors: Itsumi Arakawa, Ikunobu Muramatsu, Junsuke Uwada, Kiyonao Sada, Noriyuki Matsukawa, Takayoshi Masuoka Tags: ORIGINAL ARTICLE Source Type: research

Sialic acid biosynthesis pathway blockade disturbs neuronal network formation in human iPSC ‐derived excitatory neurons
This study shows that sialic acid is necessary for neuronal network formation during human neuronal development and provides a physiologically relevant model to study the role of sialic acid in patient-derived iNeurons. (Source: Journal of Neurochemistry)
Source: Journal of Neurochemistry - August 31, 2023 Category: Neuroscience Authors: Rachel Mijdam, Chantal Bijnagte ‐Schoenmaker, Emma Dyke, Sam J. Moons, Thomas J. Boltje, Nael Nadif Kasri, Dirk J. Lefeber Tags: ORIGINAL ARTICLE Source Type: research

Differential responses of disease ‐related GRIN variants located in pore‐forming M2 domain of N‐methyl‐D‐aspartate receptor to FDA‐approved inhibitors
Eleven disease-related missense variants inGRIN1,GRIN2A, andGRIN2B genes located in the pore-forming M2 re-entrant loop were evaluated for tolerance to genetic variation using three-dimensional structure and assessed for functional rescue pharmacology via electrophysiology. Three FDA-approved N-methyl-D-aspartate receptors (NMDAR) drugs (memantine, dextromethorphan, ketamine) were chosen based on their ability to bind near the M2 loop, potentially rectifying dysregulated NMDAR function by supplementing the reduced voltage-dependent Mg2+ block. These results provide insight into the structural determinants of FDA-approved N...
Source: Journal of Neurochemistry - August 31, 2023 Category: Neuroscience Authors: Rui Song, Jin Zhang, Riley E. Perszyk, Chad R. Camp, Weiting Tang, Varun Kannan, Jia Li, Yuchen Xu, Jiahui Chen, Yinlong Li, Steven  H. Liang, Stephen F. Traynelis, Hongjie Yuan Tags: ORIGINAL ARTICLE Source Type: research

Function and regulation of cis P ‐tau in the pathogenesis and treatment of conventional and nonconventional tauopathies
Cis –trans isomerization of protein plays an important role in protein folding, function, and degradation, which is regulated by peptidyl-proline isomerases (PPIases). The cis P-tau but not trans P-tau is resistant to protein dephosphorylation and degradation and also prone to protein aggregation and serves as an early driver of multiple neurodegenerative disease including Alzheimer disease (AD), traumatic brain injury (TBI), chronic traumatic encephalopathy (CTE), and vascular contributions to cognitive impairment and dementia (VCID). Cis P-tau antibody is the only clinical-stage therapeutic fo r AD that has shown the e...
Source: Journal of Neurochemistry - August 29, 2023 Category: Neuroscience Authors: Ruizhi Wang, Kun Ping Lu, Xiao Zhen Zhou Tags: REVIEW Source Type: research

Inflammation ‐stratified augmentation of vortioxetine with celecoxib: Results from a double‐blind, randomized, placebo‐controlled trial in major depressive disorder
This study investigates the predictive value of pre-treatment high-sensitivity C-Reactive Protein (hsCRP) stratification on the outcome of celecoxib augmentation of vortioxetine. The PREDDICT study was conducted as a randomized, double-blind, placebo-controlled 6-week trial on augmentation of vortioxetine with celecoxib between December 2017 and April 2020 at the University of Adelaide (Australia). The present analysis focusses on the question of whether the pre-treatment hsCRP measurement and stratification of patients to depression with inflammation (hsCRP>3  mg/L) or without inflammation (hsCRP ≤3 mg/L) has an ...
Source: Journal of Neurochemistry - August 28, 2023 Category: Neuroscience Authors: Erhan Kavakbasi, Emma Sampson, Natalie T. Mills, Hikaru Hori, Kathrin Schwarte, Christa Hohoff, K. Oliver Schubert, Scott R. Clark, C élia Fourrier, Bernhard T. Baune Tags: ORIGINAL ARTICLE Source Type: research

How can I measure brain acetylcholine levels in vivo? Advantages and caveats of commonly used approaches
Measurement of acetylcholine (ACh) dynamics in the brain is essential for understanding a wide range of behavioral processes, including attention, learning, memory, motivation, anxiety, mood, appetite, and reward. This review outlines a number of techniques that have been developed to measure ACh levels in the brain in vivo with a deeper focus on use of genetically-encoded fluorescent sensors coupled with fiber photometry, an accessible technique that can be used to monitor neurotransmitter release with high temporal resolution and specificity. AbstractThe neurotransmitter acetylcholine (ACh) plays a central role in the re...
Source: Journal of Neurochemistry - August 25, 2023 Category: Neuroscience Authors: Yann S. Mineur, Marina R. Picciotto Tags: REVIEW Source Type: research

GABAA receptors in epilepsy: Elucidating phenotypic divergence through functional analysis of genetic variants
This article will review the current knowledge in the field and provide recommendations for future functional analysis of genetic GABAA receptor variants. (Source: Journal of Neurochemistry)
Source: Journal of Neurochemistry - August 25, 2023 Category: Neuroscience Authors: Nathan L. Absalom, Susan X. N. Lin, Vivian W. Y. Liao, Han C. Chua, Rikke S. M øller, Mary Chebib, Philip K. Ahring Tags: REVIEW Source Type: research

Issue Information
Front coverViral infections of the central nervous system (CNS) in children often lead to debilitating neurological consequences during acute infection and also after recovery. Neural stem cells (NSCs) are often disrupted during CNS infections either directly by the virus or by antiviral immunity. As the juvenile age is a dynamic stage of postnatal neurogenesis, we sought to determine the impacts of an antiviral immune response on NSCs temporally from the juvenile age to adulthood. We found that the juvenile antiviral immune response decreased the NSC pool depending upon the stage of differentiation, with a push towards fo...
Source: Journal of Neurochemistry - August 23, 2023 Category: Neuroscience Tags: ISSUE INFORMATION Source Type: research

Fundamental neurochemistry review: Glutamatergic dysfunction as a central mechanism underlying flavivirus ‐induced neurological damage
Physiological glutamatergic transmission and flavivirus-induced pathological alterations. On average, 400 million cases of infection by flaviviruses are reported every year. Several of these viruses may cause neurologic symptoms in a subset of patients. Here, we review studies that suggest that replication of neurotropic flavivirus causes massive release of pro-inflammatory mediators leading to increased release and compromised reuptake of glutamate, ultimately causing excitotoxicity, reactive oxygen species production, and cell death. We also discuss current data suggesting that pharmacological approaches that counteract ...
Source: Journal of Neurochemistry - August 22, 2023 Category: Neuroscience Authors: Clara O. Nogueira, Tamires Rocha, Daniel F. Messor, Isis N. O. Souza, Julia R. Clarke Tags: REVIEW Source Type: research

Receptor –ligand interaction controls microglial chemotaxis and amelioration of Alzheimer's disease pathology
In this review, we highlight the importance of microglial chemotaxis in promoting the clearance of danger-associated molecular patterns in Alzheimer's disease (AD). We further discuss how microglial receptor –ligand signalings, including TREM2, CD33, IL-3/IL-3R, IL-33/ST2, and CCL2/CCR2 pathways, and the dysregulation of decoy receptor milieus impair microglial chemotaxis along AD progression. Further detailed investigations are essential to identify the molecular machinery that controls microglial ch emotaxis in AD, which facilitates the development of microglia-targeting AD therapies. AbstractMicroglia maintain brain h...
Source: Journal of Neurochemistry - August 21, 2023 Category: Neuroscience Authors: Shun ‐Fat Lau, Amy K. Y. Fu, Nancy Y. Ip Tags: REVIEW Source Type: research

Ketamine improves neuronal recovery following spreading depolarization in peri ‐infarct tissues
We examined spreading depolarization (SD) waves in a mouse stroke model. SDs were initiated by focal potassium chloride application and propagated through a region of graded perfusion deficit created by distal middle cerebral artery (dMCA) occlusion. Longer lasting depolarizations (DC shifts measured from local field potential (LFP) electrodes) and neuronal Ca2+ transients (epifluorescence GCaMP imaging) occurred at locations with larger perfusion deficits (proximal to occlusion), as compared with remote recording sites (laser speckle contrast imaging (LSCI) of cerebral perfusion). Ketamine, at concentrations that did not ...
Source: Journal of Neurochemistry - August 19, 2023 Category: Neuroscience Authors: Katelyn M. Reinhart, Russell A. Morton, K. C. Brennan, Andrew P. Carlson, C. William Shuttleworth Tags: ORIGINAL ARTICLE Source Type: research

Metabolic aspects of genetic ion channel epilepsies
There is increasing awareness of contributions of impaired brain metabolism to epilepsies. We review existing studies regarding metabolism in epilepsies caused by mutations in sodium (SCN1A) and potassium (KCNA1) channels. This is important as gene therapy is not yet available. While there are still little data about impairments of brain metabolism, the studies revealed ketogenic diets to be mostly effective, particularly for Dravet syndrome with identified SCN1A mutations as well as mouse and zebrafish models with SCN1A and KCNA1 mutations. We discuss how ketogenic diet and potentially other metabolic therapies may help t...
Source: Journal of Neurochemistry - August 18, 2023 Category: Neuroscience Authors: Elliott S. Neal, Weizhi Xu, Karin Borges Tags: REVIEW Source Type: research

Progression of reactive gliosis and astroglial phenotypic changes following stab wound ‐induced traumatic brain injury in mice
Stab wound results in a focal traumatic brain injury. Following the injury, reactive GFAP+ astrocytes can be clustered in five different reactive phenotypes (I –V) while type 0 astrocytes remain non-reactive. Type V astrocytes exhibit increased cell size, more complex morphology, and reduced expression of homeostatic genes such as glutamine synthetase and aquaporin-4. Conversely, they over-express of the pro-inflammatory molecule C3. Injection of LPS inc reases the abundance of type V astrocytes and NF-κB inhibitor sulfasalazine decreases it. We propose that type V astrocytes represent astrocytes that have undergone pat...
Source: Journal of Neurochemistry - August 18, 2023 Category: Neuroscience Authors: Maria Belen Cieri, Alejandro Villarreal, Dante Daniel Gomez ‐Cuautle, Ingrid Mailing, Alberto Javier Ramos Tags: ORIGINAL ARTICLE Source Type: research

Retraction Statement: Palmitate ‐induced C/EBP homologous protein activation leads to NF‐κB‐mediated increase in BACE1 activity and amyloid beta genesis
The above article, published online on 6th January 2018, has been retracted by agreement between the journal ‘s Editor-in-Chief Andrew J. Lawrence, Deputy Editor-in-Chief Marco A.M. Prado and John Wiley and Sons Ltd. The authors were contacted for approval of the retraction, but did not respond. The Editorial Office was recently notified of potential image manipulation. A subsequent image forensics analy sis indicated that the band in the histone H3 lane of Figure 1A and the bands in beta actin lane of Figure 3A appears similar to each other, such that one band is resized with respect to the other. Original unmodified bl...
Source: Journal of Neurochemistry - August 17, 2023 Category: Neuroscience Tags: RETRACTION Source Type: research

Issue Information
Front coverKrabbe disease (KD) is an inherited demyelinating disease caused by a genetic deficiency of the lysosomal enzyme galactosylceramide (GalCer) β-galactosidase (GALC). The major substrate for GALC is the myelin lipid GalCer. However, the pathogenesis of KD has long been explained by the accumulation of psychosine, a lyso-derivative of GalCer. TheTwitcher (Twi) mouse is a naturally occurring, genetically, and enzymatically authentic mouse model of KD. Saposin-D (Sap-D) is essential for the degradation of ceramide by acid ceramidase (ACDase) in the lysosome. Watanabe et al. revisited the “pshychosine hypothesis”...
Source: Journal of Neurochemistry - August 17, 2023 Category: Neuroscience Tags: ISSUE INFORMATION Source Type: research