المؤلفون: Hitomi Otani, Chiyoko Inagaki, Kaori Kitagawa, Zheng-Mei Xiong, Bo Wu, Nan-Yan Zhang

المصدر: Neuroscience Letters. 399:175-180

مصطلحات موضوعية: medicine.medical_specialty, Proto-Oncogene Proteins pp60(c-src), Intracellular Space, Glutamic Acid, Apoptosis, Biology, Hippocampus, Phosphatidylinositol 3-Kinases, chemistry.chemical_compound, Chlorides, Western blot, Internal medicine, Lactate dehydrogenase, medicine, Animals, Phosphorylation, Rats, Wistar, Neurotransmitter, Cells, Cultured, Neurons, Amyloid beta-Peptides, L-Lactate Dehydrogenase, medicine.diagnostic_test, General Neuroscience, Glutamate receptor, Neurotoxicity, Tyrosine phosphorylation, Embryo, Mammalian, medicine.disease, Molecular biology, Peptide Fragments, Mitochondria, Rats, Endocrinology, chemistry, Toxicity, Tyrosine, Proto-Oncogene Proteins c-akt, Intracellular

الوصف: In our previous studies, pathophysiological concentrations of amyloid-beta (Abeta) proteins increased intracellular Cl(-) concentration ([Cl(-)]i) and enhanced glutamate neurotoxicity in primary cultured neurons, suggesting Cl(-)-dependent changes in glutamate signaling. To test this possibility, we examined the effects of isethionate-replaced low Cl(-) medium on the Abeta-induced enhancement of glutamate neurotoxicity in the primary cultured rat hippocampal neurons. In a normal Cl(-) (135 mM) medium, treatment with 10 nM Abeta25-35 for 2 days increased neuronal [Cl(-)]i to a level three times higher than that of control as assayed using a Cl(-)-sensitive fluorescent dye, while in a low Cl(-) (16 mM) medium such an Abeta25-35-induced increase in [Cl(-)]i was not observed. The Abeta treatment aggravated glutamate neurotoxicity in a normal Cl(-) medium as measured by mitochondrial reducing activity and lactate dehydrogenase (LDH) release, while in a low Cl(-) medium the Abeta treatment did not enhance glutamate toxicity. Upon such Abeta plus glutamate treatment under a normal Cl(-) condition, activated anti-apoptotic molecule Akt (Akt-pS473) level monitored by Western blot significantly decreased to 74% of control. Under a low Cl(-) condition, a resting Akt-pS473 level was higher than that under a normal Cl(-) condition and did not significantly change upon Abeta plus glutamate treatment. Tyrosine phosphorylation levels of 110 and 60 kDa proteins (pp110 and pp60) increased upon Abeta plus glutamate treatment under a normal Cl(-), but not low Cl(-), condition. These findings indicated that Abeta-induced enhancement of glutamate neurotoxicity is Cl(-)-dependent. Chloride-sensitive Akt pathway and tyrosine phosphorylation of proteins (pp110 and pp60) may be involved in this process.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::b569ea98ea47ea175dfa11af2e40ad9eTest
https://doi.org/10.1016/j.neulet.2006.01.055Test

المؤلفون: Antonio G. García, Javier Egea, Mónica Sobrado, Manuela G. López, José M. Roda

المصدر: Neuroscience Letters. 365:132-136

مصطلحات موضوعية: Male, medicine.medical_specialty, In Vitro Techniques, Hippocampus, Neuroprotection, Rats, Sprague-Dawley, chemistry.chemical_compound, Memantine, Internal medicine, Lactate dehydrogenase, medicine, Galantamine, Animals, Vascular dementia, L-Lactate Dehydrogenase, General Neuroscience, medicine.disease, Acetylcholinesterase, Cell Hypoxia, Rats, Glucose, Neuroprotective Agents, Nicotinic agonist, Endocrinology, chemistry, NMDA receptor, medicine.drug

الوصف: Recent clinical trials have shown that galantamine is efficacious in the treatment of mild to moderate Alzheimer's and vascular dementia, and memantine in severe stages of these diseases. Hence, the hypothesis that these two drugs might exert different degrees of neuroprotection has been tested. Rat hippocampal slices were subjected to oxygen and glucose deprivation (OGD) and to a re-oxygenation period. Neuronal damage was monitored using the lactate dehydrogenase (LDH) released into the Krebs-bicarbonate medium as an indicator. Galantamine, a mild acetylcholinesterase (AChE) blocker and nicotinic receptor modulator, given 30 min before and during OGD plus re-oxygenation (1, 2 and 3 h) significantly reduced LDH release by around 50%. Galantamine 5 microM reduced LDH release significantly during the re-oxygenation period while at 15 microM it afforded significant reduction of LDH release both during OGD and re-oxygenation. Memantine, a reversible blocker of NMDA receptors, at 10 microM only significantly reduced (40%) LDH release after 3 h re-oxygenation. The classical NMDA blocker MK-801 reduced LDH released around 40% at 1 microM at all re-oxygenation times studied. These data indicate that galantamine has a neuroprotective window against anoxia wider than memantine. Whether these differences can be clinically relevant remain to be studied in appropriate clinical trials.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::a689f3b4861a5a11c28449aa4ee01655Test
https://doi.org/10.1016/j.neulet.2004.04.067Test

المؤلفون: Saeed Mehrabani, Robert D. Pearlstein, Donald H. Penning, Ellen M. Lockhart, Rose-Mary Boustany, David S. Warner

المصدر: Neuroscience Letters. 328:33-36

مصطلحات موضوعية: medicine.medical_specialty, N-Methylaspartate, Neuroactive steroid, Cell Survival, Neurotoxins, Excitotoxicity, Apoptosis, Cell Count, Pregnanolone, medicine.disease_cause, Neuroprotection, Membrane Potentials, chemistry.chemical_compound, Pregnancy, Internal medicine, Lactate dehydrogenase, Excitatory Amino Acid Agonists, In Situ Nick-End Labeling, Tumor Cells, Cultured, medicine, Humans, Progesterone, Fluorescent Dyes, Neurons, Asphyxia Neonatorum, TUNEL assay, Dose-Response Relationship, Drug, L-Lactate Dehydrogenase, General Neuroscience, Allopregnanolone, Infant, Newborn, Carbocyanines, Mitochondria, Neuroprotective Agents, Endocrinology, chemistry, Hypoxia-Ischemia, Brain, Amino acid neurotransmitter, NMDA receptor, Benzimidazoles, Female, Dizocilpine Maleate, Excitatory Amino Acid Antagonists

الوصف: Progesterone modulates gamma-aminobutyric acid and excitatory amino acid neurotransmitter systems and has neuroprotective properties in models of hypoxia-ischemia. This study examined the in vitro effects of allopregnanolone, the active progesterone metabolite, in models of N-methyl-D-aspartate (NMDA)-induced necrosis and apoptosis. Cultured NT2 neurons were exposed to 1 mM NMDA. Lactate dehydrogenase (LDH) release was measured 24 h later. NMDA at a concentration of 1 mM produced a 39 +/- 19% release of total LDH. Exposure to 10 microM allopregnanolone prior to NMDA exposure reduced LDH release by 51% (P = 0.0028). NMDA stimulated apoptotic cell changes defined by terminal dUTP nick-end labeling (TUNEL) and 5,5', 6,6'-tetrachloro-1,1,3,3'-tetra ethlybenzimidazolycarbocyanide iodide staining were reduced to baseline values by both 10 microM allopregnanolone and 100 microM MK-801. Pretreatment with allopregnanolone (0-10 microM) reduced the percentage of TUNEL-positive cells in a dose-dependent manner (EC(50) = 2.7 +/- 0.1 nM). Physiologic concentrations of allopregnanolone provided protection against both necrotic and apoptotic injury induced by NMDA excitotoxicity.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::60ed09654e935c2dc73da6d40531fd51Test
https://doi.org/10.1016/s0304-3940Test(02)00448-2

المؤلفون: Brandi Reeves, Todd F. Glass, Frank R. Sharp

المصدر: Neuroscience Letters. 328:133-136

مصطلحات موضوعية: medicine.medical_specialty, Traumatic brain injury, Central nervous system, Cell Culture Techniques, Ischemia, chemistry.chemical_compound, Fetus, Pregnancy, Physical Stimulation, Tensile Strength, Internal medicine, Lactate dehydrogenase, Neurites, medicine, Animals, Axon, Coloring Agents, Hypoxia, Brain, Cells, Cultured, Neurons, Cell Death, L-Lactate Dehydrogenase, business.industry, General Neuroscience, Brain, Membranes, Artificial, Trypan Blue, Hypoxia (medical), medicine.disease, Biomechanical Phenomena, Rats, Disease Models, Animal, medicine.anatomical_structure, Endocrinology, chemistry, Brain Injuries, Female, Trypan blue, Neuron, medicine.symptom, business, Neuroscience

الوصف: In traumatic brain injury, the brain is subjected to mechanical shear and varying degrees of hypoxia/ischemia. To compare effects of stretch injury, hypoxia, and the combination of both insults on neurons, mixed neuronal and astrocytic cultures were established from day 17 fetal rat brains. On days 17-19 in vitro, cultures were subjected to stretch injury or hypoxia of varying degrees, alone and in combination. Cultures were assayed for lactate dehydrogenase release and Trypan Blue uptake. Hypoxia or Stretch injury alone induced a graded response (P0.05) on both assays. Stretch+Hypoxia (4 or 6 h) resulted in significantly greater injury as compared with controls (P0.05), and as compared with either isolated Stretch or Hypoxia (1, 2, 4 or 6 h) alone (P0.05).

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::eccc85c888356f8d52de02ed93033b3bTest
https://doi.org/10.1016/s0304-3940Test(02)00510-4

المؤلفون: Xiaoming Li, Yingcai Niu, Li Zhou, Miaoxian Dong, Ying-Bo Zhang, Jicheng Liu, Gang Wang

المصدر: Neuroscience Letters. 487:88-93

مصطلحات موضوعية: medicine.medical_specialty, Programmed cell death, Cell Survival, Neurotoxins, Apoptosis, Pharmacology, PC12 Cells, Neuroprotection, Drug Administration Schedule, chemistry.chemical_compound, Puerarin, Annexin, Internal medicine, medicine, Animals, Drug Interactions, MTT assay, Annexin A5, Enzyme Inhibitors, Dose-Response Relationship, Drug, L-Lactate Dehydrogenase, biology, Caspase 3, General Neuroscience, Cytochrome c, JNK Mitogen-Activated Protein Kinases, Neurotoxicity, medicine.disease, Isoflavones, Rats, Neuroprotective Agents, Endocrinology, nervous system, chemistry, 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine, biology.protein, Signal Transduction

الوصف: Apoptosis is a widely accepted component of the pathogenesis of Parkinson's disease (PD), a debilitating neurodegenerative disorder characterized by loss of dopaminergic neurons in the substantia nigra. In this study, we investigated the neuroprotective effects of puerarin and possible mechanisms by which puerarin acts against MPP(+)-induced toxicity in rat pheochromocytoma PC12 cells. PC12 cells exposed to MPP(+) (500 μM) significantly decreased the viability of PC12 cells when examined by MTT assay, DNA ELISA assay, and Annexin V assays, which was prevented by puerarin in a dose-dependent manner. PC12 cells exposed to MPP(+) (500 μM) elicited phosphorylation of MKK7, c-Jun-NH(2)-terminal kinase (JNK), and c-Jun which followed by the increase in cytochrome c levels, and which was prevented by puerarin. Moreover, puerarin inhibited the activation of caspase-9 and caspase-3 in MPP(+)-exposed PC12 cells. Whereas, the neuroprotective effect of puerarin against MPP(+) insults can be blocked by SP600125 (inhibitor of JNK). Taken together, these results suggest that puerarin protected PC12 cells against MPP(+)-induced neurotoxicity through the inhibition of the JNK signaling pathways. Therefore, puerarin has the possible beneficial effects in PD by attenuating MPP(+)-induced toxicity.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::663302e37d49e8ea392f5fea0a75ebb7Test
https://doi.org/10.1016/j.neulet.2010.10.002Test

المؤلفون: Jeremy D. Coplan, Peter J. Bergold, Anna Jozwicka, Diana Dow-Edwards, Ning Zhao, André A. Fenton, Hsin-Yi Kao, Maryam Syed, Valariya Pinkhasova

المصدر: Neuroscience Letters. 453:219-224

مصطلحات موضوعية: medicine.medical_specialty, Central nervous system, Action Potentials, Hippocampus, Hippocampal formation, Biology, Redox, Injections, Sodium Lactate, chemistry.chemical_compound, Cerebrospinal fluid, Internal medicine, Lactate dehydrogenase, Pyruvic Acid, medicine, Animals, Rats, Long-Evans, Neurons, General Neuroscience, Metabolism, NAD, Rats, medicine.anatomical_structure, Endocrinology, chemistry, Biochemistry, Lactates, Panic Disorder, NAD+ kinase, Oxidation-Reduction

الوصف: Lactate uses an unknown mechanism to induce panic attacks in people and panic-like symptoms in rodents. We tested whether intraperitoneal (IP) lactate injections act peripherally or centrally to induce panic-like symptoms in rats by examining whether IP lactate directly affects the CNS. In Long-Evans rats, IP lactate (2 mmol/kg) injection increased lactate levels in the plasma and the cerebrospinal fluid. IP lactate also induced tachycardia and behavioral freezing suggesting the production of panic-like behavior. To enter intermediate metabolism, lactate is oxidized by lactate dehydrogenase (LDH) to pyruvate with co-reduction of NAD + to NADH. Therefore, we measured the ratio of NADH/NAD + to test whether IP lactate altered lactate metabolism in the CNS. Lactate metabolism was studied in the hippocampus, a brain region believed to contribute to panic-like symptoms. IP lactate injection lowered the ratio of NADH/NAD + without altering the total amount of NADH and NAD + suggesting oxidation of hippocampal redox state. Lactate oxidized hippocampal redox since intrahippocampal injection of the LDH inhibitor, oxamate (50 mM) prevented the oxidation of NADH/NAD + by IP lactate. In addition to oxidizing hippocampal redox, IP lactate rapidly increased the firing rate of hippocampal neurons. Similar IP pyruvate injections had no effect. Neural discharge also increased following intrahippocampal lactate injection suggesting that increased discharge was a direct action of lactate on the hippocampus. These studies show that oxidation of brain redox and increased hippocampal firing are direct actions of lactate on the CNS that may contribute to the production of lactate-induced panic.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::5f11549c60adaaaa0c1eb0466f656716Test
https://doi.org/10.1016/j.neulet.2009.02.041Test

المؤلفون: Jean-Yuan Yu, Hsueh-Meei Huang, Hsio-Chung Ou, Kee Ching Jeng

المصدر: Neuroscience Letters. 438:252-256

مصطلحات موضوعية: Brain Infarction, MAPK/ERK pathway, Receptors, Steroid, medicine.medical_specialty, MAP Kinase Signaling System, Proto-Oncogene Proteins c-jun, Narcotic Antagonists, Ischemia, medicine.disease_cause, PC12 Cells, c-Fos, Nitric oxide, chemistry.chemical_compound, Internal medicine, Nuclear Receptor Subfamily 4, Group A, Member 1, medicine, Animals, Enzyme Inhibitors, Genes, Immediate-Early, Neurons, Mitogen-Activated Protein Kinase 3, L-Lactate Dehydrogenase, biology, Naloxone, General Neuroscience, Hypoxia (medical), medicine.disease, Rats, DNA-Binding Proteins, Oxidative Stress, Neuroprotective Agents, Endocrinology, Gene Expression Regulation, chemistry, Cytoprotection, Reperfusion Injury, Hypoxia-Ischemia, Brain, biology.protein, Encephalitis, medicine.symptom, Proto-Oncogene Proteins c-fos, Immediate early gene, Reperfusion injury, Oxidative stress

الوصف: Cerebral ischemia/reperfusion involves inflammatory process and naloxone is able to reduce infarct volume and has been used as a therapeutic agent for brain injury. Hypoxia induces the immediate early genes (IEGs) rapidly and transiently that may initiate a cascade of cellular responses that are necessary for survival and normal function. However, the protective effect of naloxone on ischemic/hypoxic neuronal cells was only partly studied. Thus, the effects of naloxone on oxygen- and glucose-deprivation (OGD) and OGD followed by reoxygenation (OGD/R) on the expression of IEGs were examined in PC12 cells. The result showed that lactate dehydrogenase (LDH) released in the media was reduced by naloxone. The temporal response of IEG mRNA encoding c-fos, c-jun, nur77, and zif268 was induced with different degree of intensity following hypoxia, whereas the level of GAPDH mRNA was relatively constant. However, these signals of c-fos, c-jun, and nur77 by hypoxia were reduced significantly by naloxone. Treatment with OGD also activated mitogen-activated protein kinase (MAPK) pathway. The induction of c-fos, c-jun, nur77, and zif268 by hypoxia was inhibited by naloxone (0.1 microM) and MAPK inhibitors (10 microM of U0126, D98059, SB203580). However, naloxone increased the expression of ERK1/2 by OGD concomitantly diminished the LDH release. Thus, the present studies demonstrated that OGD induced IEGs including c-fos, c-jun, nur77, and zif268 and MAPK signaling pathways were regulated differently by naloxone.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::13ed20126681ba6b02a887ebfe91a025Test
https://doi.org/10.1016/j.neulet.2008.04.036Test

المؤلفون: Oliver S. Kempski, Klaus Lowitzsch, John F. Stover

المصدر: Neuroscience Letters. 238:25-28

مصطلحات موضوعية: Adult, Male, medicine.medical_specialty, Multiple Sclerosis, Excitotoxicity, Glutamic Acid, medicine.disease_cause, Xanthine, Spinal Cord Diseases, chemistry.chemical_compound, Cerebrospinal fluid, Central Nervous System Diseases, Albumins, Lactate dehydrogenase, Internal medicine, medicine, Humans, Lactic Acid, Xanthine oxidase, Chromatography, High Pressure Liquid, Serum Albumin, Hypoxanthine, Epilepsy, L-Lactate Dehydrogenase, General Neuroscience, Glutamate receptor, Middle Aged, Meningitis, Viral, Uric Acid, Cerebrovascular Disorders, Endocrinology, chemistry, Biochemistry, Uric acid, Female

الوصف: Glutamate-mediated excitotoxicity is associated with adenosine triphosphate (ATP) degradation and generation of oxygen radicals. Hypoxanthine and lactate depict energetic impairment, while xanthine and uric acid reflect activity of radical producing xanthine oxidase. Cerebrospinal fluid (CSF) glutamate, hypoxanthine, lactate, xanthine, and uric acid were investigated in neurological patients. In multiple sclerosis, myelopathy, stroke, epilepsy and viral meningitis glutamate, hypoxanthine, xanthine, and uric acid are increased 2-3-fold compared to controls. Lactate is only elevated in meningitis. Normal lactate dehydrogenase (LDH) levels and absent correlation between the albumin ratio and neurochemical parameters exclude an artificial increase due to cell lysis and barrier damage. Absent correlation between neurochemical parameters within each patient group is most likely related to preserved glial and neuronal uptake mechanisms. CSF hypoxanthine, xanthine, and uric acid levels appear superior to lactate in reflecting glutamate-mediated excitotoxicity in neurological patients.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::6d63d77c765d68f3ecc41ce25fd05395Test
https://doi.org/10.1016/s0304-3940Test(97)00840-9

المؤلفون: David A. Cox, Marlene L. Cohen

المصدر: Neuroscience Letters. 229:37-40

مصطلحات موضوعية: medicine.medical_specialty, Cell Survival, Neurotoxins, Peptide, Biology, Hippocampal formation, Hippocampus, chemistry.chemical_compound, Internal medicine, Lactate dehydrogenase, Phospholipase D, medicine, Animals, Cells, Cultured, Neurons, chemistry.chemical_classification, Amyloid beta-Peptides, L-Lactate Dehydrogenase, General Neuroscience, Neurotoxicity, medicine.disease, In vitro, Rats, Enzyme Activation, enzymes and coenzymes (carbohydrates), Enzyme, Endocrinology, chemistry, Colorimetry, lipids (amino acids, peptides, and proteins), Phosphatidylethanol

الوصف: The role of phospholipase D (PLD) in amyloid beta (Abeta)-induced neurotoxicity was studied by comparing the effects of Abeta (1-40) on PLD activity and release of lactate dehydrogenase (LDH) from cultured rat hippocampal cells. PLD activity was determined in [3H]myristic acid-labeled cells by measuring the formation of [3H]phosphatidylethanol in the presence of ethanol (0.5%), and LDH activity in the cell media was measured via colorimetric assay. Abeta (50 microM), aged for 3 days to allow for peptide aggregation, acutely (1 h) stimulated PLD activity. Unaged Abeta (50 microM) had no acute (1 h) effect on PLD activity, but significantly stimulated PLD activity by 87% when incubated with cells for 1-3 days. Abeta (50 microM)-induced PLD activity was closely correlated with Abeta (50 microM)-induced LDH release over a time course of 1-3 days. These data suggest that PLD activation may be involved in Abeta-induced neurotoxicity.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::91c9c4cba4c5b601893b73e47f015a73Test
https://doi.org/10.1016/s0304-3940Test(97)00407-2

المؤلفون: Won Ki Kim, Young Sook Pae

المصدر: Neuroscience Letters. 216:117-120

مصطلحات موضوعية: medicine.medical_specialty, Cerebellum, Free Radicals, Homocysteine, medicine.drug_class, Prefrontal Cortex, Biology, Receptors, N-Methyl-D-Aspartate, Antioxidants, Rats, Sprague-Dawley, Superoxide dismutase, chemistry.chemical_compound, Internal medicine, Lactate dehydrogenase, medicine, Animals, Mannitol, Cells, Cultured, 6-Cyano-7-nitroquinoxaline-2,3-dione, Neurons, Cell Death, L-Lactate Dehydrogenase, Superoxide Dismutase, General Neuroscience, Neurotoxicity, Hydrogen Peroxide, Catalase, medicine.disease, Receptor antagonist, Diuretics, Osmotic, Rats, Endocrinology, medicine.anatomical_structure, 2-Amino-5-phosphonovalerate, nervous system, chemistry, CNQX, biology.protein, NMDA receptor, Calcium, Excitatory Amino Acid Antagonists

الوصف: The present study investigates the possible mechanism responsible for the neurotoxicity of d,l -homocysteine in primary culture of rat cerebellar granule cells. Neurotoxicity was assessed by measuring the amount of lactate dehydrogenase released from the cells following homocysteine treatment. d,l -Homocysteine (> 300 μM; 16–22 h) induced the release of lactate dehydrogenase from the cells in a concentration-dependent manner. The N -methyl- d -aspartate (NMDA) antagonist (±)-2-amino-5-phosphonopentanoic acid (APV) partially blocked the homocysteine-mediated neurotoxicity. However, the non-NMDA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) did not block the homocysteine-mediated toxicity. The homocysteine-mediated neurotoxicity was mostly prevented by the co-administration of superoxide dismutase and catalase or catalase alone. The results suggest that homocysteine induces neuronal cell death by stimulating NMDA receptor as well as by producing free radicals.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::189acc1f8f88921df3cdad96bca41331Test
https://doi.org/10.1016/0304-3940Test(96)13011-1