Protective Effect of High Glucose Against Ischemia-Induced Synaptic Transmission Damage in Rat Hippocampal Slices

2002 ◽  
Vol 88 (1) ◽  
pp. 236-248 ◽  
Author(s):  
Guo-Feng Tian ◽  
Andrew J. Baker
Keyword(s):  
Synaptic Transmission ◽  
Pyramidal Cell ◽  
High Glucose ◽  
Glucose Concentration ◽  
Cell Layer ◽  
Hippocampal Slices ◽  
Excitatory Postsynaptic Potential ◽  
Pyramidal Cell Layer ◽  
Before And After

Cerebral ischemic damage is an important cause of morbidity and mortality. However, there is conflicting evidence regarding the effect of the extracellular glucose concentration in focal and global ischemic injury. This study was designed to investigate this effect in ischemia-induced synaptic transmission damage in rat hippocampal slices. Slices were superfused with artificial cerebrospinal fluid (ACSF) containing various concentrations of glucose before and after ischemia. The evoked somatic postsynaptic population spike (PS) and dendritic field excitatory postsynaptic potential (fEPSP) were extracellularly recorded in the CA1 stratum pyramidal cell layer and s. radiatum after stimulation of the Schaeffer collaterals, respectively. The glucose concentration in ACSF before and after ischemia determined the duration of ischemia tolerated by synaptic transmission as demonstrated by complete recovery of the somatic PS and dendritic fEPSP. Specifically, the somatic PS and dendritic fEPSP completely recovered following 3, 4, and 5 min of ischemia only when slices were superfused with ACSF containing 4, 10, and 20 mM glucose before and after ischemia, respectively. The latencies of the somatic and dendritic ischemic depolarization (ID) occurrence in the CA1 s. pyramidal cell layer and s. radiatum were significantly longer with 10 than 4 mM glucose in ACSF before ischemia and significantly longer with 20 than 10 mM glucose in ACSF before ischemia. Regardless of the glucose concentration in ACSF before and after ischemia, the somatic PS and dendritic fEPSP only partially recovered when ischemia was terminated at the occurrence of ID. These results indicate that high glucose in ACSF during the period before and after ischemia significantly protects CA1 synaptic transmission against in vitro ischemia-induced damage through postponing the occurrence of ID.

Glycolysis Prevents Anoxia-Induced Synaptic Transmission Damage in Rat Hippocampal Slices

2000 ◽  
Vol 83 (4) ◽  
pp. 1830-1839 ◽  
Author(s):  
Guo-Feng Tian ◽  
Andrew J. Baker
Keyword(s):  
Synaptic Transmission ◽  
Anaerobic Metabolism ◽  
Cell Layer ◽  
Hippocampal Slices ◽  
Sodium Cyanide ◽  
Artificial Cerebrospinal Fluid ◽  
Elevated Glucose ◽  
Chemical Anoxia ◽  
Stimulation Of

Prolonged anoxia can cause permanent damage to synaptic transmission in the mammalian CNS. We tested the hypothesis that lack of glucose is the major cause of irreversible anoxic transmission damage, and that anoxic synaptic transmission damage could be prevented by glycolysis in rat hippocampal slices. The evoked population spike (PS) was extracellularly recorded in the CA1 pyramidal cell layer after stimulation of the Schaffer collaterals. When the slice was superfused with artificial cerebrospinal fluid (ACSF) containing 4 mM glucose, following 10 min anoxia, the evoked PS did not recover at all after 60 min reoxygenation. When superfusion ACSF contained 10 mM glucose with or without 0.5 mM α-cyano-4-hydroxycinnate (4-CIN), after 60 min reoxygenation the evoked PS completely recovered following 10 min anoxia. When superfusion ACSF contained 20 mM glucose with or without 1 mM sodium cyanide (NaCN), after 60 min reoxygenation the evoked PS completely recovered even following 120 min anoxia. In contrast, when superfusion ACSF contained 4 mM glucose, following 10 min 1 mM NaCN chemical anoxia alone, without anoxic anoxia, the evoked PS displayed no recovery after 60 min reoxygenation. Moreover, when 16 mM mannitol and 16 sodiuml-lactate were added into 4 mM glucose ACSF, following 10 min anoxia the evoked PS failed to recover at all after 60 min reoxygenation. The results indicate that elevated glucose concentration powerfully protected the synaptic transmission against anoxic damage, and the powerful protection is due to anaerobic metabolism of glucose and not a result of the higher osmolality in higher glucose ACSF. We conclude that lack of glucose is the major cause of anoxia-induced synaptic transmission damage, and that if sufficient glucose is supplied, glycolysis could prevent this damage in vitro.

Accumulation of apolipoprotein E and β-amyloid-like protein in a trace of the hippocampal CA1 pyramidal cell layer after ischaemic delayed neuronal death

Neuroreport ◽  
1996 ◽  
Vol 7 (18) ◽  
pp. 3063-3068 ◽  
Author(s):  
Hirohisa Ishimaru ◽  
Koichi Ishikawa ◽  
Seiichi Haga ◽  
Mikio Shoji ◽  
Yoshihide One ◽  
...  
Keyword(s):  
Apolipoprotein E ◽  
Pyramidal Cell ◽  
Neuronal Death ◽  
Cell Layer ◽  
Delayed Neuronal Death ◽  
Pyramidal Cell Layer ◽  
Hippocampal Ca1 ◽  
Β Amyloid

scholarly journals Sulodexide reduces glucose induced senescence in human retinal endothelial cells

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
A. Gericke ◽  
K. Suminska-Jasińska ◽  
A. Bręborowicz
Keyword(s):  
Endothelial Cells ◽  
High Glucose ◽  
Glucose Concentration ◽  
Chronic Exposure ◽  
Replicative Senescence ◽  
Population Doubling ◽  
Population Doubling Time ◽  
High Glucose Concentration ◽  
Retinal Endothelial Cells

AbstractChronic exposure of retinal endothelium cells to hyperglycemia is the leading cause of diabetic retinopathy. We evaluated the effect of high glucose concentration on senescence in human retinal endothelial cells (HREC) and modulation of that effect by Sulodexide. Experiments were performed on HREC undergoing in vitro replicative senescence in standard medium or medium supplemented with glucose 20 mmol/L (GLU) or mannitol 20 mnol/L (MAN). Effect of Sulodexide 0.5 LRU/mL (SUL) on the process of HREC senescence was studied. Glucose 20 mmol/L accelerates senescence of HREC: population doubling time (+ 58%, p < 0.001) β-galactosidase activity (+ 60%, p < 0.002) intracellular oxidative stress (+ 65%, p < 0.01), expression of p53 gene (+ 118%, p < 0.001). Senescent HREC had also reduced transendothelial electrical resistance (TEER) (− 30%, p < 0.001). Mannitol 20 mmol/L used in the same scenario as glucose did not induce HREC senescence. In HREC exposed to GLU and SUL, the senescent changes were smaller. HREC, which became senescent in the presence of GLU, demonstrated higher expression of genes regulating the synthesis of Il6 and VEGF-A, which was reflected by increased secretion of these cytokines (IL6 + 125%, p < 0.001 vs control and VEGF-A + 124% p < 0.001 vs control). These effects were smaller in the presence of SUL, and additionally, an increase of TEER in the senescent HREC was observed. Chronic exposure of HREC to high glucose concentration in medium accelerates their senescence, and that process is reduced when the cells are simultaneously exposed to Sulodexide. Additionally, Sulodexide decreases the secretion of IL6 and VEGF-A from senescent HREC and increases their TEER.

Brain lactic acidosis and synaptic function

1990 ◽  
Vol 68 (2) ◽  
pp. 164-169 ◽  
Author(s):  
Wolfgang Walz ◽  
Diane E. Harold
Keyword(s):  
Lactic Acid ◽  
Synaptic Transmission ◽  
Hippocampal Slices ◽  
Sodium Lactate ◽  
Extracellular Ph ◽  
Synaptic Function ◽  
Excitatory Postsynaptic Potential ◽  
Irreversible Damage ◽  
Acid Release ◽  
Neuronal Transmission

Measurements of the presynaptic fiber volley (PSFV), the population excitatory postsynaptic potential (EPSP), and the extracellular pH in the dendritic CA1 layer of rat hippocampal slices were used to evaluate the effects of lactacidosis on central synaptic transmission. Replacement of NaCl with sodium lactate (up to 30 mM) was found not to affect the PSFV; however, the EPSP was reversibly suppressed. Sodium citrate, with added CaCl2 to adjust for Ca2+ chelation, had the same effect as sodium lactate. Addition of lactic acid influenced the PSFV only when, at a concentration of 30 mM, the extracellular pH dropped to 6.6 or lower. With lactic acid concentrations of up to 20 mM, which produced pH levels of 6.8 in the slice, effects on the EPSP were reversible. However, 30 mM lactic acid suppressed both the PSFV and EPSP irreversibly. These results show that synaptic transmission is much more susceptible to lactacidosis than presynaptic axonal transmission. They also show that high levels of lactate, albeit causing suppression of synaptic transmission, do not cause irreversible damage. However, acidosis associated with lactic acid release may damage synaptic transmission irreversibly.Key words: acidosis, hippocampal slice, ischemia, lactate, lactic acid, neuronal transmission, synapse.

scholarly journals High glucose induces early senescence in adipose-derived stem cells by accelerating p16 and mTOR

2019 ◽  
Vol 6 (6) ◽  
pp. 3213-3221
Author(s):  
Hieu Liem Pham ◽  
Phuc Van Pham
Keyword(s):  
Stem Cells ◽  
High Glucose ◽  
Glucose Concentration ◽  
Culture Medium ◽  
Diabetic Patients ◽  
Adipose Derived Stem Cells ◽  
Differentiation Potential ◽  
Normal Glucose

Introduction: The senescence of stem cells is the primary reason that causes aging of stem cell-containing tissues. Some hypotheses have suggested that high glucose concentration in diabetic patients is the main factor that causes senescence of cells in those patients. This study aimed to evaluate the effects of high glucose concentrations on the senescence of adipose-derived stem cells (ADSCs). Methods: ADSCs were isolated and expanded from human adipose tissues. They were characterized and confirmed as mesenchymal stem cells (MSCs) by expression of surface markers, their shape, and in vitro differentiation potential. They were then cultured in 3 different media- that contained 17.5 mM, 35 mM, or 55 mM of D-glucose. The senescent status of ADSCs was recorded by the expression of the enzyme beta-galactosidase, cell proliferation, and doubling time. Real-time RT-PCR was used to evaluate the expression of p16, p21, p53 and mTOR. Results: The results showed that high glucose concentrations (35 mM and 55 mM) in the culture medium induced senescence of human ADSCs. The ADSCs could progress to the senescent status quicker than those cultured in the lower glucose-containing medium (17.5 mM). The senescent state was related to the up-regulation of p16 and mTOR genes. Conclusion: These results suggest that high glucose in culture medium can trigger the expression of p16 and mTOR genes which cause early senescence in ADSCs. Therefore, ADSCs should be cultured in low glucose culture medium, or normal glucose concentration, to extend their life in vitro as well as in vivo.  

Functional Characterization of Des-IGF-1 Action at Excitatory Synapses in the CA1 Region of Rat Hippocampus

2005 ◽  
Vol 94 (1) ◽  
pp. 247-254 ◽  
Author(s):  
Melinda M. Ramsey ◽  
Michelle M. Adams ◽  
Olusegun J. Ariwodola ◽  
William E. Sonntag ◽  
Jeff L. Weiner
Keyword(s):  
Synaptic Transmission ◽  
Hippocampal Slices ◽  
Functional Characterization ◽  
Excitatory Postsynaptic Potential ◽  
Excitatory Synapses ◽  
Aged Rats ◽  
Cognitive Improvement ◽  
Ca1 Region

Insulin-like growth factor-1 (IGF-1) and growth hormone play a major role in the growth and development of tissues throughout the mammalian body. Plasma IGF-1 concentrations peak during puberty and decline with age. We have determined that chronic treatments to restore plasma IGF-1 concentrations to adult levels attenuate spatial learning deficits in aged rats, but little is known of the acute actions of IGF-1 in the brain. To this end, we utilized hippocampal slices from young Sprague-Dawley rats to characterize the acute effects of des-IGF-1 on excitatory synaptic transmission in the CA1 region. We observed a 40% increase in field excitatory postsynaptic potential (fEPSP) slope with application of des-IGF-1 (40 ng/ml) and used whole cell patch-clamp recordings to determine that this enhancement was due to a postsynaptic mechanism involving α-amino-3-hydroxyl-5-methyl-4-isoxazolepropionate (AMPA) but not N-methyl-d-aspartate receptors. Furthermore, the enhancement was completely blocked by the broad-spectrum tyrosine kinase inhibitor, genistein (220 μM), and significantly reduced by the PI3K blockers wortmannin (1 μM) and 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one (10 μM), suggesting that the effect was predominantly dependent on PI3K activation. This characterization of the acute actions of des-IGF-1 at hippocampal excitatory synapses may provide insight into the mechanism by which long-term increases in plasma IGF-1 impart cognitive benefits in aged rats. Increases in AMPA receptor-mediated synaptic transmission may contribute directly to cognitive improvement or initiate long-term changes in synthesis of proteins such as brain-derived neurotrophic factor that are important to learning and memory.

Novel Form of Long-Term Synaptic Depression in Rat Hippocampus Induced By Activation of α1 Adrenergic Receptors

2004 ◽  
Vol 91 (2) ◽  
pp. 1071-1077 ◽  
Author(s):  
Cary L. Scheiderer ◽  
Lynn E. Dobrunz ◽  
Lori L. McMahon
Keyword(s):  
Synaptic Transmission ◽  
Receptor Antagonist ◽  
Adrenergic Receptors ◽  
Hippocampal Slices ◽  
Low Frequency ◽  
Adrenergic System ◽  
Normal Cognitive Function ◽  
Dependent Learning

Neurons located in the locus coeruleus project to hippocampus and provide noradrenergic innervation necessary for hippocampal-dependent learning and memory. The mechanisms underlying the function of norepinephrine (NE) in memory processing are unknown but likely reside in the ability of NE to modulate the efficacy of glutamate synaptic transmission via activation of G-protein-coupled adrenergic receptors. Here we show that application of NE to rat hippocampal slices in vitro induces a long-term depression (LTD) of synaptic transmission at excitatory CA3–CA1 synapses that persists for ≥40 min after agonist washout. This LTD, which we refer to as NE LTD, is mediated by activation of α1 adrenergic receptors because the α1 agonist methoxamine can induce LTD at the same magnitude as that induced with the nonselective adrenergic agonist NE. Furthermore, NE LTD induced by either NE or methoxamine is blocked with the α1 receptor antagonist, prazosin, but is unaffected by antagonists of α2 and β receptors. This plasticity persists in the presence of the GABAA receptor antagonist bicuculline, indicating that adrenergic modulation of GABAA receptor-mediated transmission does not underlie NE LTD. Induction of NE LTD requires presynaptic activity during agonist application and postsynaptic activation of N-methyl-d-aspartate receptors, fulfilling Hebbian criteria of coincident pre- and postsynaptic activity. The expression of NE LTD is likely to be postsynaptic because paired-pulse facilitation ratios during NE LTD expression are not different from baseline, similar to LTD induced by low-frequency stimulation. Thus we report the identification and characterization of a novel Hebbian form of LTD in hippocampus that is induced after activation of α1 adrenergic receptors. This plasticity may be a mechanism by which the adrenergic system participates in normal cognitive function.

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