Biomedical subjects

S Tekkök

Publications and source records attributed to S Tekkök.

7 recordsLinked to original sources

PubMed1999

Diabetes mellitus preserves synaptic plasticity in hippocampal slices from middle-aged rats.

Synaptic plasticity is generally believed to provide a cellular mechanism for learning and memory. One manifestation of synaptic plasticity, long-term potentiation in the CA1 region, was compared in hippocampal slices from young and older rats, both control animals and streptozotocin-treated diabetics with moderate hyperglycemia ( approximately 15 mM). Long-term potentiation of excitatory synaptic potentials, elicited by tetanic stimulation or by 2-deoxy-D-glucose application, was readily obtained in slices from young (four-month-old) control and diabetic rats, but not in slices from middle-aged (12-month-old) control rats. Both forms of potentiation, however, could be elicited in slices from 12-month-old diabetics. The unexpected finding that long-term potentiation is restored in moderately hyperglycemic older rats suggests that the blood glucose level of older animals may be important for synaptic plasticity and perhaps for the ability to learn.

Aging↗

PubMed1999

Intraneuronal [Ca2+] changes induced by 2-deoxy-D-glucose in rat hippocampal slices.

Temporary replacement of glucose by 2-deoxyglucose (2-DG; but not sucrose) is followed by long-term potentiation of CA1 synaptic transmission (2-DG LTP), which is Ca2+-dependent and is prevented by dantrolene or N-methyl--aspartate (NMDA) antagonists. To clarify the mechanism of action of 2-DG, we monitored [Ca2+]i while replacing glucose with 2-DG or sucrose. In slices (from Wistar rats) kept submerged at 30 degreesC, pyramidal neurons were loaded with [Ca2+]-sensitive fluo-3 or Fura Red. The fluorescence was measured with a confocal microscope. Bath applications of 10 mM 2-DG (replacing glucose for 15 +/- 0.38 min, means +/- SE) led to a rapid but reversible rise in fluo-3 fluorescence (or drop of Fura Red fluorescence); the peak increase of fluo-3 fluorescence (DeltaF/F0), measured near the end of 2-DG applications, was by 245 +/- 50% (n = 32). Isosmolar sucrose (for 15-40 min) had a smaller but significant effect (DeltaF/F0 = 94 +/- 14%, n = 10). The 2-DG-induced DeltaF/F0 was greatly reduced (to 35 +/- 15%, n = 16) by,-aminophosphono-valerate (50-100 microM) and abolished by 10 microM dantrolene (-4.0 +/- 2.9%, n = 11). A substantial, although smaller effect, of 2-DG persisted in Ca2+-free 1 mM ethylene glycol-bis(beta-aminoethyl ether)-N,N,N', N'-tetraacetic acid (EGTA) medium. Two adenosine antagonists, which do not prevent 2-DG LTP, were also tested; 2-DG-induced DeltaF/F0 (fluo-3) was not affected by the A1 antagonist 8-cyclopentyl-3, 7-dihydro-1,3-dipropyl-1H-purine-2,6-dione (DPCPX 50 nM; 287 +/- 38%; n = 20), but it was abolished by the A1/A2 antagonist 8-SPT; 25 +/- 29%, n = 19). These observations suggest that 2-DG releases glutamate and adenosine and that the rise in [Ca2+] may be triggered by a synergistic action of glutamate (acting via NMDA receptors) and adenosine (acting via A2b receptors) resulting in Ca2+ release from a dantrolene-sensitive store. The discrepant effects of sucrose and 8-SPT on DeltaF/F0, on the one hand, and 2-DG LTP, on the other, support other evidence that increases in postsynaptic [Ca2+]i are not essential for 2-DG LTP.

Animals↗

PubMed1998

Higher sensitivity of CA1 synapses to aglycemia in streptozotocin-diabetic rats is age-dependent.

We studied conduction velocity in peripheral nerves and the block of synaptic transmission produced by lack of glucose in hippocampal slices from 4- and 12-month-old streptozotocin-induced diabetic rats and their age-matched controls. In sural nerves of young and old diabetic rats, the conduction velocity was reduced by 30-35%. In slices from young diabetics, CA1 synaptic transmission was more sensitive to aglycemia than in control slices. However, all slices from older rats showed comparable increases in CA1 synaptic sensitivity to aglycemia. We conclude that the cerebral adaptation to diabetic hyperglycemia apparent in the hippocampus of young rats is masked in older rats by an age-dependent increase in sensitivity to lack of glucose.

Adenosine↗

PubMed1997

2-Deoxy-D-glucose-induced changes in membrane potential, input resistance, and excitatory postsynaptic potentials of CA1 hippocampal neurons.

Temporary block of glycolysis by 2-deoxy-D-glucose (2-DG) reversibly suppresses synaptic transmission in the CA1 region of hippocampal slices. Recovery of responses is followed by a sustained potentiation of field excitatory postsynaptic potentials (EPSPs) (2-DG-LTP). To investigate the mechanisms involved in this type of LTP, we studied the effects of 2-DG on membrane properties of CA1 neurons (in slices from Sprague-Dawley rats), recorded with sharp intracellular electrodes containing 3 M KCl, as well as patch electrodes, filled mainly with 150 mM KMeSO4 and Hepes. The predominant change produced by 15- to 20-min applications of 2-DG (10 mM, replacing glucose) was hyperpolarization (-5.6 +/- 1.1 mV for 18 intracellular recordings and -7.2 +/- 0.80 mV for 17 whole-cell recordings) accompanied by a fall in resistance (-33 +/- 2.5% for 14 intracellular recordings and -11.6 +/- 7.1% for 15 whole-cell recordings). Virtually identical hyperpolarizations were recorded in the presence of 20 microM glyburide (-5.5 +/- 1.5 mV, n = 6), but they were abolished by adenosine antagonists 8-(p-sulfophenyl)theophylline (8-SPT) and 8-cyclopentyl-3,7-dihydro-1,3-dipropyl-1H-purine-2,6-dione (DPCPX) (2.8 +/- 1.6 and 4.0 +/- 1.7 mV, respectively; n = 5 for both). It was concluded that the hyperpolarization is most likely caused by an increase in K+ conductance, activated by a 2-DG-induced rise in adenosine release. After such applications of 2-DG, a sustained potentiation of EPSPs (similar to the 2-DG-LTP of field EPSPs) was evident in five neurons recorded with intracellular electrodes but not in any of nine whole-cell recordings, where it was replaced by sustained, LTD-like depression. We conclude that a factor essential for 2-DG-LTP induction is lost during whole-cell recording.

Animals↗

PubMed1996

Calcium dependence of LTP induced by 2-deoxyglucose in CA1 neurons.

1. As previously reported, in hippocampal slices from Sprague-Dawley rats, 13-min applications of 2-deoxy-D-glucose (2-DG) (substituting 10 mM 2-DG for glucose)-which sharply depress field excitatory postsynaptic potentials (EPSPs)-are followed by a sustained potentiation of the initial slopes of EPSPs (2-DG-LTP). 2. Such 2-DG-LTP is not prevented by exposing slices to Ca(2+)-free medium for 25 min before the 13-min 2-DG applications (in Ca(2+)-free medium). Therefore 2-DG-LTP is not dependent on influx of external Ca2+ during the 2-DG applications. 3. When the Ca(2+)-free conditions begin 15 min before, and are maintained for 10 min after, the 13-min 2-DG applications (in Ca(2+)-free medium), 2-DG-LTP is either totally suppressed or much reduced. A delayed Ca2+ influx thus plays a crucial role in the induction of 2-DG-LTP. 4. Much longer Ca(2+)-free pretreatment (for 77 min) largely abolishes 2-DG-LTP. Therefore Ca2+ release from a compartment (presumably intracellular) that is not readily depleted is also important for the induction of 2-DG-LTP. 5. This intracellular Ca2+ store is sensitive to dantrolene sodium (10 microM)-which prevents 2-DG-LTP-but not 10 microM thapsigargin. 2-DG-LTP of isolated N-methyl-D-aspartate-receptor-mediated EPSPs is only partly reduced by dantrolene. 6. Dantrolene (10 microM) also reduces or abolishes posttetanic potentiation, but not paired-pulse facilitation. 7. Depotentiation by 1-Hz stimulation is abolished by 20 microM dantrolene. 8. In contrast to the above, long-term potentiation (LTP) elicited by tetanic stimulation is prevented by 10 microM thapsigargin but not by dantrolene (< or = 50 microM). 9. In conclusion, two mechanisms of intracellular Ca2+ concentration increase appear to be essential for LTP induction by 2-DG. One is Ca2+ influx after the 2-DG application; the other is Ca2+ release from a dantrolene-sensitive internal store. The opposite effects of thapsigargin and dantrolene on 2-DG-LTP and tetanic LTP suggest that distinct internal sources of Ca2+ may be needed for the induction of these two forms of LTP.

Animals↗

PubMed1995

Long-term potentiation in hippocampal slices induced by temporary suppression of glycolysis.

1. Temporary suppression of glycolysis by 2-deoxy-D-glucose (2-DG)-long enough to abolish CA1 population spikes (PSs) and reduce field excitatory postsynaptic potentials (EPSPs) by two-thirds-is followed by a sustained rebound of EPSPs and PSs (both up by 70-150%). 2. Post 2-DG long-term potentiation (2-DG-LTP) is prevented by block of N-methyl-D-aspartate (NMDA) receptors (NMDARs). Though 2-DG-LTP is normally expressed by other receptors, in presence of picrotoxin 2-DG causes similar LTP of NMDAR-mediated EPSPs. 3. Stimulation at 1 s-1 fully depotentiates 2-DG-LTP. 4. Unlike tetanic LTP, 2-DG-LTP is not pathway-specific, is not occluded by a preceding tetanic LTP (or vice versa) and is insensitive to block of NO synthesis. 5. Hypoglycemic states may have long-lasting after-effects on cerebral synaptic function.

Animals↗

PubMed1994

Preventive effect of intracisternal heparin for proliferative angiopathy after experimental subarachnoid haemorrhage in rats.

Proliferative angiopathy represents the morphological basis of delayed cerebral vasospasm. The initial vasoconstriction and endothelial damage of the vasospastic arteries leads to an exaggerated response of the smooth muscle cells within the media leading to subintimal thickening and myonecrosis. Heparin reduces the exposure of the media to platelet derived growth factor, a mitogen from aggregating platelets responsible for the migration and proliferation of the myofibroblasts. Since systemic heparin in the setting of a subarachnoid haemorrhage would be unacceptable, we have tested the effect of heparin on proliferative angiopathy by injecting autologous non-heparinized blood into two groups of rats (N = 12 each) and then inject the heparin into the spinal fluid of one group after one hour. We were able to show histologically that intracisternal heparin injection after the subarachnoid haemorrhage has reduced the vascular wall changes to a great degree. Heparinization of the cerebrospinal fluid carried out in conjunction with early operation for aneurysms may be a promising approach to prevent the morbid complications of SAH in the clinical setting.

Animals↗