Moderate hypoglycemia aggravates effects of hypoxia in hippocampal slices from diabetic rats
Section snippets
Experimental procedures
STZ, dissolved in citrate buffer at pH 4 (Rerup, 1970, Mans et al., 1988), was injected into 4-week-old male Wistar rats (Charles River, Canada; 65 mg/kg i.p.). All developed clear signs of diabetes, including polyuria, polydipsia, glucosuria, cataracts and moderate hyperglycemia: 3 months after injecting STZ, blood glucose levels were 14±1.5 mM (vs. 4–6 mM in control rats). On average, the diabetic rats weighed 30% less than their age-matched controls.
Following procedures approved by the
Results
In Fig. 1, Fig. 2, Fig. 3, Fig. 4 are illustrated data obtained from the four groups of slices: controls and diabetics in 10 and 4 mM glucose, respectively. In each figure, the inset traces (above) are examples from a single slice obtained (a) during the initial control period, (b) after virtual disappearance of the fEPSP, (c) at the end of the hypoxic period (when the AV was also lost) and (d) 15–30 min later when recovery was near maximal (at times indicated by arrows in the graphs below).
Synaptic transmission in slices from control rats
Because input–output plots cover a wide range of EPSP amplitudes, they provide a good overall index of the efficacy of transmission (Andersen et al., 1980). By this criterion, under ‘normoxic’ conditions (95% O2) transmission was not different in control slices equilibrated in ACSF containing 10 or 4 mM glucose. This is in agreement with other evidence that, within the range 3–10 mM, transmission is rather insensitive to [G] (p. 401 in Dingledine, 1984, Schurr et al., 1989, Izumi and Zorumski,
Acknowledgements
With support from the Medical Research Council of Canada, la Commission Québec-Communauté Française de Belgique and the FNRS Belgium. We are grateful to Drs. J. Križ and A. Padjen for their help in preparing diabetic rats.
References (84)
- et al.
Functional characteristics of unmyelinated fibres in the hippocampal cortex
Brain Res.
(1978) - et al.
Impact of diabetes on CNS: role of signal transduction cascade
Brain Res. Bull.
(1999) - et al.
Defective activity of Na+, K(+)-ATPase in peripheral nerve of diabetic rats is independent of the axonal transport of the enzyme
Neurosci. Lett.
(1994) Cerebral complications of diabetes: clinical findings and pathogenetic mechanisms
Neth. J. Med.
(1999)- et al.
Water maze learning and hippocampal synaptic plasticity in streptozotocin-diabetic rats treatment
Brain Res.
(1998) - et al.
Chronic hyperglycaemia increases neuronal sensitivity to high potassium in hippocampal slices from streptozotocin-treated diabetic rats
Neurosci. Lett.
(2000) - et al.
Neuronal excitability and conduction velocity changes in hippocampal slices from streptozotocin-treated diabetic rats
Brain Res.
(2000) Calcium-mediated neurotoxicity: relationship to specific channel types and role in ischemic damage
Trends Neurosci.
(1988)- et al.
Diminished ouabain-sensitive, sodium-potassium ATPase activity in sciatic nerves of rats with streptozotocin-induced diabetes
Exp. Neurol.
(1976) - et al.
A hypoxic injury potential in the hippocampal slice
Brain Res.
(1988)
Purine release and inhibition of synaptic transmission during hypoxia and hypoglycemia in rat hippocampal slices
Neurosci. Lett.
ATP-sensitive K+ channel effects on nerve function, Na+, K+ ATPase, and glutathione in diabetic rats
Eur. J. Pharmacol.
Effects of changes in glucose concentration on synaptic plasticity in hippocampal slices
Brain Res.
Adenosine antagonists prevent hypoxia-induced depression of excitatory but not inhibitory synaptic currents
Neurosci. Lett.
Progressive cortical atrophy after forebrain ischemia in diabetic rats
Neurosci. Res.
Effects of streptozotocin-induced hyperglycemia on brain damage following transient ischemia
Neurobiol. Dis.
Hippocampal slices from long-term streptozotocin-injected rats are prone to epileptiform responses
Neurosci Lett.
Glucose regulation and cognitive functions: relation to Alzheimer’s disease and diabetes
Behav. Brain Res.
Extracellular space structure revealed by diffusion analysis
Trends Neurosci.
Increased damage after ischemic stroke in patients with hyperglycemia with or without established diabetes mellitus
Am. J. Med.
Recovery of synaptic transmission predicted from extracellular K+ undershoots following brief anoxia in hippocampal slices
Brain Res.
Glucose enhances recovery of potassium ion homeostasis and synaptic excitability in rat hippocampal slices exposed to brief anoxia
Brain Res.
A high glucose environment improves survival of diabetic neurons in culture
Neurosci. Lett.
Increased glucose improves recovery of neuronal function in the hippocampal slice preparation
Brain Res.
Electrophysiology of energy metabolism and neuronal function in the hippocampal slice preparation
J. Neurosci. Methods
Extracellular potassium ion activity and electrophysiology in the hippocampal slice: paradoxical recovery of synaptic transmission during anoxia
Brain Res.
The neurologic implications of diabetic hyperglycemia during surgical procedures at increased risk for brain ischemia
J. Clin. Anesth.
Higher sensitivity of CA1 synapses to aglycemia in streptozotocin-diabetic rats is age-dependent
Brain Res.
Alterations in the properties and isoform ratios of brain Na+/K(+)-ATPase in streptozotocin diabetic rats
Biochim. Biophys. Acta
Adenosine release is a major cause of failure of synaptic transmission during hypoglycaemia in rat hippocampal slices
Neurosci. Lett.
Persistent block of CA1 synaptic function by prolonged hypoxia
Neuroscience
Possible mechanisms for long-lasting potentiation of synaptic transmission in hippocampal slices from guinea-pigs
J. Physiol. (Lond.)
The transport of glucose into the brain of the rat in vivo
Proc. R. Soc. Lond. B
Mechanisms activating glycolysis in the brain in arterial hypoxia
J. Neurochem.
Cerebral function in diabetes mellitus
Diabetologia
PO2-profiles in hippocampal slices of the guinea pig
Exp. Brain Res.
Sugar transport across the blood-brain barrier
Am. J. Physiol.
Reduced adenosine uptake accelerates ischaemic block of population spikes in hippocampal slices from streptozotocin-treated diabetic rats
Eur. J. Neurosci.
Impaired modulation of AMPA receptors by calcium-dependent processes in streptozotocin-induced diabetic rats
Brain Res.
Effects of hypoxia and normocarbia on cerebral blood flow and metabolism in conscious man
J. Appl. Physiol.
Mitochondria and calcium: from cell signalling to cell death
J. Physiol. (Lond.)
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Present address: Department of Neurology, University of Washington, Seattle, WA 98195, USA