المؤلفون: Shengzhou Wu, Steven W. Barger

المصدر: Journal of Neurochemistry. 138:503-505

مصطلحات موضوعية: 0301 basic medicine, biology, Gliotransmitter, medicine.disease, Biochemistry, Serine, 03 medical and health sciences, Cellular and Molecular Neuroscience, DISC1, Glutamatergic, 030104 developmental biology, 0302 clinical medicine, Schizophrenia, mental disorders, biology.protein, medicine, NMDA receptor, Neurochemistry, Receptor, Neuroscience, 030217 neurology & neurosurgery

الوصف: This Editorial highlights a study by Xia and coworkers in the current issue of the Journal of Neurochemistry, in which the authors reveal a possible mechanistic link between DISC1 (disrupted-in-schizophrenia-1), a genetic risk factor for schizophrenia, and N-methyl-d-aspartate receptor (NMDAR) that is also linked with schizophrenia. The authors show that perturbed communication between DISC1 and NMDARs represents a hidden perpetrator for abnormal dendritic and synaptic maturation. Read the highlighted article 'DISC1, astrocytes and neuronal maturation: a possible mechanistic link with implications for mental disorders' on page 518.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::b8d45319cac064ec6f53c92a579d0abaTest
https://doi.org/10.1111/jnc.13699Test

المؤلفون: Yun-feng Zhang, Liping Song, Yimei Liu, Xianwei Wang, Haiyan Jiang, Junxu Fang, Mengjuan Wu, Shifeng Li, Shengzhou Wu

المصدر: Journal of neurochemistry. 143(3)

مصطلحات موضوعية: 0301 basic medicine, Lipopolysaccharides, Vascular Endothelial Growth Factor A, Angiogenesis, Racemases and Epimerases, Mice, Transgenic, Retinal Pigment Epithelium, Blindness, Nitric Oxide, Biochemistry, Nitric oxide, 03 medical and health sciences, Cellular and Molecular Neuroscience, chemistry.chemical_compound, Mice, 0302 clinical medicine, medicine, Serine, Animals, RNA, Messenger, Cells, Cultured, biology, Lasers, Macrophages, Retinal, Anatomy, Molecular biology, eye diseases, Choroidal Neovascularization, Endothelial stem cell, Nitric oxide synthase, Mice, Inbred C57BL, Disease Models, Animal, 030104 developmental biology, Choroidal neovascularization, chemistry, Gene Expression Regulation, Serine racemase, Mutation, 030221 ophthalmology & optometry, biology.protein, Cytokines, sense organs, medicine.symptom, Ex vivo

الوصف: Choroidal neovascularization (CNV) is a leading cause of blindness in age-related macular degeneration. Production of VEGF and macrophage recruitment by retinal pigment epithelial cells (RPE) significantly contributes to the process of CNV in an experimental CNV model. Serine racemase (SR) is expressed in retinal neurons and glial cells, and its product, D-serine, is an endogenous co-agonist of N-methyl-D-aspartate receptor (NMDAR). Activation of the receptor results in production of nitric oxide (.NO), a molecule that promotes retinal and choroidal neovascularization. These observations suggest possible roles of SR in CNV. With laser-injured CNV mice, we found that inactivation of SR-coding gene (Srrnull) significantly reduced CNV volume, neovascular density, and invading macrophages. We exploited the underlying mechanism in vivo and ex vivo. RPE from wild-type (WT) mice expressed SR. To explore the possible downstream target of SR inactivation, we showed that choroid/RPE homogenates extracted from laser-injured Srrnull mice contained less inducible nitric oxide synthase (iNOS) and decreased phospho-VEGFR2 compared to amounts in WT mice. In vitro, inflammation-primed WT RPEs expressed more iNOS, produced more .NO and VEGF than did inflammation-primed Srrnull RPEs. When co-cultured with inflammation-primed Srrnull RPE, significantly fewer RF/6A-a cell line of choroidal endothelial cell (CEC), migrated to the opposite side of the insert membrane than did cells co-cultured with pre-treated WT RPE. Altogether, SR deficiency reduces RPE response to laser-induced inflammatory stimuli, resulting in decreased production of a cascade of pro-angiogenic cytokines, including .NO and VEGF, and reduced macrophage recruitment, which contribute synergistically to attenuated angiogenesis. This article is protected by copyright. All rights reserved.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::9f7ff0eb72f551cdc264f4fa8dc1b75eTest
https://pubmed.ncbi.nlm.nih.gov/32530094Test

المؤلفون: Krista L. Moulder, Krzysztof L. Hyrc, Shengzhou Wu, Timothy Warmke, B. Joy Snider, Ying Lin

المصدر: Journal of Neurochemistry. 109:1225-1236

مصطلحات موضوعية: medicine.medical_specialty, Programmed cell death, Patch-Clamp Techniques, Time Factors, Leupeptins, Biophysics, Neocortex, Cysteine Proteinase Inhibitors, Endoplasmic Reticulum, Biochemistry, Article, Membrane Potentials, Amiloride, Lactones, Mice, Cellular and Molecular Neuroscience, Cytosol, Calcium imaging, Internal medicine, Excitatory Amino Acid Agonists, medicine, Animals, Uniporter, Cells, Cultured, Caspase, Neurons, Membrane potential, Cell Death, Dose-Response Relationship, Drug, biology, Endoplasmic reticulum, 3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester, Calcium Channel Blockers, Embryo, Mammalian, Electric Stimulation, Cell biology, Endocrinology, Cell Death Process, Astrocytes, biology.protein, Calcium, Proteasome Inhibitors, Sesquiterpenes

الوصف: Cytosolic Ca(2+) concentration ([Ca(2+)](i)) is reduced in cultured neurons undergoing neuronal death caused by inhibitors of the ubiquitin proteasome system. Activation of calcium entry via voltage-gated Ca(2+) channels restores cytosolic Ca(2+) levels and reduces this neuronal death (Snider et al. 2002). We now show that this reduction in [Ca(2+)](i) is transient and occurs early in the cell death process, before activation of caspase 3. Agents that increase Ca(2+) influx such as activation of voltage-gated Ca(2+) channels or stimulation of Ca(2+) entry via the plasma membrane Na-Ca exchanger attenuate neuronal death only if applied early in the cell death process. Cultures treated with proteasome inhibitors had reduced current density for voltage-gated Ca(2+) channels and a less robust increase in [Ca(2+)](i) after depolarization. Levels of endoplasmic reticulum Ca(2+) were reduced and capacitative Ca(2+) entry was impaired early in the cell death process. Mitochondrial Ca(2+) was slightly increased. Preventing the transfer of Ca(2+) from mitochondria to cytosol increased neuronal vulnerability to this death while blockade of mitochondrial Ca(2+) uptake via the uniporter had no effect. Programmed cell death induced by proteasome inhibition may be caused in part by an early reduction in cytosolic and endoplasmic reticulum Ca(2+,) possibly mediated by dysfunction of voltage-gated Ca(2+) channels. These findings may have implications for the treatment of disorders associated with protein misfolding in which proteasome impairment and programmed cell death may occur.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::47be7d5445536748fc2f989bdfeb66f6Test
https://doi.org/10.1111/j.1471-4159.2009.06037.xTest

المؤلفون: Yuhua Chang, Haiyan Jiang, Meiling Feng, He Zhang, Xianwei Wang, Shengzhou Wu

المصدر: Journal of neurochemistry. 136(1)

مصطلحات موضوعية: 0301 basic medicine, Male, Retinal Ganglion Cells, N-Methylaspartate, Excitotoxicity, Racemases and Epimerases, Mice, Transgenic, medicine.disease_cause, Biochemistry, Retinal ganglion, Retina, 03 medical and health sciences, Cellular and Molecular Neuroscience, chemistry.chemical_compound, Mice, 0302 clinical medicine, medicine, Excitatory Amino Acid Agonists, Animals, TUNEL assay, Chemistry, Retinal, Molecular biology, eye diseases, Mice, Inbred C57BL, 030104 developmental biology, medicine.anatomical_structure, Retinal ganglion cell, Serine racemase, Intravitreal Injections, Mutation, NMDA receptor, Female, sense organs, 030217 neurology & neurosurgery

الوصف: Convincing data demonstrate that D-serine, a racemized product of serine racemase (SR), contributes to neurotoxicity. Furthermore, a line of evidence suggests that SR/D-serine contributes to retinal neurodegeneration in a diabetic retinopathy rat model and diabetic retinopathy patients. However, the connection between SR/D-serine and retinal neurodegeneration remains unclear. Herein, we report that intravitreal injection of N-methyl-D-aspartate (NMDA) induces excitotoxicity in rodent retina; this retinal neurodegeneration was attenuated in retina carrying a loss-of-function of mutation in Srr, the gene for SR, termed Srr(ochre269). Under the condition of NMDA injection, either posterior pole or middle - but not peripheral - retina from Srr(ochre269) mice was found to retain more retinal ganglion cells (RGC) than the counterpart from w/t (RGCs were identified with retrograde labeling). Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining further demonstrated reduced RGC apoptosis from Srr(ochre269) compared to w/t mice under the condition of NMDA injection. Collectively, our studies demonstrate a pivotal role of SR/D-serine in retinal neurotoxicity. We demonstrated that loss-of-function mutation of the gene encoding serine racemase significantly attenuates excitotoxicity in retina; excitotoxicity accounts for retinal ganglion cell (RGC) demise in diabetic retinopathy (DR). We think that our findings deepen the current knowledge of the mechanisms of RGC degeneration.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::cb33f4808bcfaec986fa6ba125edb9baTest
https://pubmed.ncbi.nlm.nih.gov/26485193Test