Brain energy metabolism: A roadmap for future research
This article details current knowledge and major unknowns in brain energy metabolism and lays out a roadmap for future research. AbstractAlthough we have learned much about how the brain fuels its functions over the last decades, there remains much still to discover in an organ that is so complex. This article lays out major gaps in our knowledge of interrelationships between brain metabolism and brain function, including biochemical, cellular, and subcellular aspects of functional metabolism and its imaging in adult brain, as well as during development, aging, and disease. The focus is on unknowns in metabolism of major b...
Source: Journal of Neurochemistry - January 7, 2024 Category: Neuroscience Authors: Caroline D. Rae,
Joseph A. Baur,
Karin Borges,
Gerald Dienel,
Carlos Manlio Díaz‐García,
Starlette R. Douglass,
Kelly Drew,
João M. N. Duarte,
Jordi Duran,
Oliver Kann,
Tibor Kristian,
Dasfne Lee‐Liu,
Britta E. Lindquist,
Ewan C. M Tags: ORIGINAL ARTICLE Source Type: research
Transforming growth factor ‐β1 protects against white matter injury and reactive astrogliosis via the p38 MAPK pathway in rodent demyelinating model
Brain stereotactic injection of LPC leads to local robust demyelination and reactive astrogliosis in the corpus callosum of mice. Supplementary TGF- β1 binds to its receptor TGF-βRI/II and then promotes the translocation of downstream molecule Smad3 into the nuclei. As a transcription factor, activated Smad3 regulates the expression of corresponding genes (such as MAG and MBP) to exert subsequent functions. Specifically, activation of TGF-β1 pathway accelerates the maturation and migration processes of OLs, and restores the reactive astrogliosis probably through regulating the p38 MAPK signal pathway. Ultimately, supple...
Source: Journal of Neurochemistry - January 6, 2024 Category: Neuroscience Authors: Yi Xie,
Xuejiao Chen,
Xinyue Wang,
Shuai Liu,
Simiao Chen,
Zhiyuan Yu,
Wei Wang Tags: ORIGINAL ARTICLE Source Type: research
Over ‐expression of N‐acetylaspartate synthase exacerbates pathological energetic deficit and accelerates cognitive decline in the 5xFAD mouse
Increasing NAA synthase (Nat8L) via AAV-mediated overexpression in a model of Alzheimer ’s Disease compromises mitochondrial energy metabolism. Sequestration of mitochondrial aspartate by NAA is incompatible with pathological energetic crisis, accelerates associated cognitive decline and presents a rationale for the active reduction of NAA in a broad clinical spectrum of neurodegener ative disease.Image content: Overexpression of NAA synthase (Nat8L) in hippocampal Neurons of 5xFAD mice compounds phenotypic energy deficit and accelerates cognitive decline. AbstractN-acetylaspartate (NAA) is an abundant central nervous sy...
Source: Journal of Neurochemistry - January 6, 2024 Category: Neuroscience Authors: Jeremy S. Francis,
Quy Nguyen,
Vladimir Markov,
Paola Leone Tags: ORIGINAL ARTICLE Source Type: research
Metal dyshomeostasis in the substantia nigra of patients with Parkinson's disease or multiple sclerosis
This study aimed to compare the intra- and extra-neuronal metal content and the expression of proteins related to metal homeostasis in the substantia nigra (SN) from patients with Parkinson's disease (PD), multiple sclerosis (MS), and control subjects. Metal quantification was performed via ion-beam micro-analysis in neuromelanin-positive neurons and the surrounding tissue. For proteomic analysis, SN tissue lysates were analyzed on a nanoflow chromatography system hyphenated to a hybrid triple-quadrupole time-of-flight mass spectrometer. We found increased amounts of iron in neuromelanin-positive neurons and surrounding ti...
Source: Journal of Neurochemistry - January 5, 2024 Category: Neuroscience Authors: Asuncion Carmona,
Eleonora Carboni,
Lucas Caldi Gomes,
St éphane Roudeau,
Fabian Maass,
Christof Lenz,
Richard Ortega,
Paul Lingor Tags: ORIGINAL ARTICLE Source Type: research
L ‐ascorbyl‐2‐phosphate alleviates white matter injury caused by chronic hypoxia through the PRMT5/P53/NF‐κB pathway
This study aimed to explore the protective effects of AS-2P against chronic hypoxia-induced WMI, and elucidate the underlying mechanisms. An in vivo chronic hypoxia model and in vitro oxygen–glucose deprivation (OGD) model were established to explore the effects of AS-2P on WMI using immunofluorescence, immunohistochemistry, western blotting, real-time quantitative polymerase chain reaction, Morris water maze test, novel object recogni tion test, beaming-walking test, electron microscopy, and flow cytometry. The results showed that AS-2P resulted in the increased expression of MBP, Olig2, PDGFRα and CC1, improved thi...
Source: Journal of Neurochemistry - January 4, 2024 Category: Neuroscience Authors: Bingqing Ding,
Jia Lou,
Tianqi Qin,
Weiwei Xie,
Di Li,
Peijun Li,
Xingyun Wang,
Zhenlang Lin,
Xiaoling Guo,
Jianghu Zhu Tags: ORIGINAL ARTICLE Source Type: research
Accumulation of extracellular elastin ‐derived peptides disturbed neuronal morphology and neuron–microglia crosstalk in aged brain
Extracellular elastin fibers were degraded irreversibly in the aging brain, increasing sensitivity to stroke, vascular dementia, and Alzheimer's disease. The role of physiologically active elastin-derived peptides (EDPs) in neurons is currently being studied. It was suggested that release and accumulation of EDPs lead to neuronal spine loss and microglial hyperactivation. Galectin (Gal-3) secretion from stressed neurons was engaged in the neurons-microglia crosstalk, which promoted microglia engulfment. Synapse loss and local neuroinflammatory processes would contribute to neurological symptoms associated with neurodegener...
Source: Journal of Neurochemistry - January 3, 2024 Category: Neuroscience Authors: Jun Ma,
Bingqian Wang,
Xiaoxi Wei,
Meng Tian,
Xingfu Bao,
Yifan Zhang,
Huichuan Qi,
Yi Zhang,
Min Hu Tags: ORIGINAL ARTICLE Source Type: research
Resveratrol differentially affects MMP ‐9 release from neurons and glia; implications for therapeutic efficacy
“Resveratrol has differential effects on neuronal and glial MMP release” As shown above, resveratrol inhibits basal and LPS-stimulated release of MMP2/9 from cultured glia, which may promote BBB injury, but spares basal and NMDA-stimulated MMP-9 release from neurons, which may promote neuronal p lasticity. Of interest, however, resveratrol reduces PNN component expression from both culture types. AbstractResveratrol, a naturally occurring polyphenol that activates sirtuin 1 (SIRT1), has been shown to reduce overall levels of matrix metalloprotease-9 (MMP-9) in cerebrospinal fluid (CSF) samples from patients with Alzhei...
Source: Journal of Neurochemistry - January 2, 2024 Category: Neuroscience Authors: Matthew Amontree,
Matthew Nelson,
Lara Stefansson,
Daniel Pak,
Kathleen Maguire ‐Zeiss,
R. Scott Turner,
Katherine Conant Tags: ORIGINAL ARTICLE Source Type: research
From molecules to behavior: Implications for perineuronal net remodeling in learning and memory
Perineuronal nets (PNNs) are condensed extracellular matrix structures consisting of multiple components joined together in a lattice-like fashion around particular neurons. In general, PNNs are thought to restrict plasticity (e.g., closure of critical periods, stabilization of synapses, and refinement of neural activity), subsequently impacting learning and memory processes. PNNs are highly dynamic and continuously fluctuate in composition and distribution throughout life and in response to various contexts, rendering them as a substrate for experience- and disease-dependent cognitive function. AbstractPerineuronal nets (...
Source: Journal of Neurochemistry - December 31, 2023 Category: Neuroscience Authors: Brenda Sanchez,
Piotr Kraszewski,
Sabrina Lee,
Elise C. Cope Tags: REVIEW Source Type: research
Issue Information
Front coverGaucher disease (GD) is a lysosomal storage disorder (LSD) caused by the defective activity of acid β-glucosidase (GCase) which results from mutations in GBA1. Neurological forms of GD (nGD) can be generated in mice by intra-peritoneal injection of conduritol B-epoxide (CBE) which irreversibly inhibits GCase. Unlike transcriptomics, proteomics gives direct information about protein expression whi ch is more likely to provide insight into which cellular pathways are impacted in disease. We performed non-targeted, mass spectrometry based quantitative proteomics on brains from mice injected with CBE. Differentiall...
Source: Journal of Neurochemistry - December 29, 2023 Category: Neuroscience Tags: ISSUE INFORMATION Source Type: research
MMP ‐2‐mediated Scube2 degradation promotes blood–brain barrier disruption by blocking the interaction between astrocytes and endothelial cells via inhibiting Sonic hedgehog pathway during early cerebral ischemia
In this issue, we demonstrate that MMP-2 could degrade astrocytic Scube2 and contribute to ischemic BBB disruption. The findings are as follows: (1) ischemia induces Scube2 degradation and MMP-2 has a direct interaction with Scube2 in astrocytes; (2) knockdown of Scube2 in astrocytes exacerbates BBB injury and downregulates Shh signaling pathway; (3) MMP-2 inhibition or overexpression of Scube2 in astrocytes protects endothelial cells from ischemic injury by activation of Shh signaling. We think these data provides a significant mechanistic understanding of the role of MMP-2 in stroke-induced loss of Scube2 and impaired Sh...
Source: Journal of Neurochemistry - December 27, 2023 Category: Neuroscience Authors: Tengrui Shi,
Shiqin Yue,
Cong Xie,
Xiaofeng Li,
Dexin Yang,
Linghui Hu,
Yunxue Zhong,
Yuan Zhang,
Wenlan Liu Tags: ORIGINAL ARTICLE Source Type: research
The efficacy of the analgesic GlyT2 inhibitor, ORG25543, is determined by two connected allosteric sites
In this study, we have characterized the mechanism of ORG25543 inhibition of GlyT2 by first considering three potential ligand binding sites on GlyT2 —the substrate site, the vestibule allosteric site and the lipid allosteric site. The three sites were tested using a combination of molecular dynamics simulations and analysis of the inhibition of glycine transport of a series point mutated GlyT2 using electrophysiological methods. We demonstrate that the lipid allosteric site on GlyT2 is the most likely binding site for ORG25543. We also demonstrate that cholesterol derived from the cell membrane can form specific interac...
Source: Journal of Neurochemistry - December 23, 2023 Category: Neuroscience Authors: Ryan Cantwell Chater,
Ada S. Quinn,
Katie Wilson,
Zachary J. Frangos,
Patrick Sutton,
Srinivasan Jayakumar,
Christopher L. Cioffi,
Megan L. O'Mara,
Robert J. Vandenberg Tags: ORIGINAL ARTICLE Source Type: research
Acknowledgement of reviewers
(Source: Journal of Neurochemistry)
Source: Journal of Neurochemistry - December 22, 2023 Category: Neuroscience Tags: ACKNOWLEDGEMENT TO REVIEWERS Source Type: research
Issue Information
Front coverWe have previously demonstrated that a cortical stroke causes persistent impairment of hippocampal-dependent cognitive tasks concomitant with secondary neurodegenerative processes such as amyloid- β accumulation in the hippocampus, a region remote from the primary
infarct. There is emerging evidence suggesting that deposition of amyloid-β around cerebral vessels may lead to cerebrovascular structural changes, neurovascular dysfunction, and disruption of blood-brain barrier integrity. Howeve r, there is limited knowledge about the temporal changes of hippocampal cerebrovasculature after cortical stroke. In the ...
Source: Journal of Neurochemistry - December 21, 2023 Category: Neuroscience Tags: ISSUE INFORMATION Source Type: research
Increases in anterograde axoplasmic transport in neurons of the hyper ‐glutamatergic, glutamate dehydrogenase 1 (Glud1) transgenic mouse: Effects of glutamate receptors on transport
In conclusion, endogenous activity at glutamate synapses regulates and glutamate synaptic hyperactivity increases intraneuronal transport rates in CNS neurons. (Source: Journal of Neurochemistry)
Source: Journal of Neurochemistry - December 21, 2023 Category: Neuroscience Authors: Phil Lee,
Jieun Kim,
In ‐Young Choi,
Ranu Pal,
Dongwei Hui,
Joanne K. Marcario,
Mary L. Michaelis,
Elias K. Michaelis Tags: ORIGINAL ARTICLE Source Type: research
Gut microbiota modification by diosgenin mediates antiepileptic effects in a mouse model of epilepsy
This study suggests that diosgenin plays a role in modifying gut microbiota, contributing to the alleviation of intestinal inflammation and neuroinflammation, ultimately inhibiting epilepsy progression in a PTZ-induced mouse model. Diosgenin emerges as a potential therapeutic option for managing epilepsy and its associated comorbidities. (Source: Journal of Neurochemistry)
Source: Journal of Neurochemistry - December 20, 2023 Category: Neuroscience Authors: Xinyu Li,
Jing Li,
Jia Ji,
Saisai Li,
Xiaoyu Yao,
Hongbin Fan,
Ruiqin Yao Tags: ORIGINAL ARTICLE Source Type: research
