Endogenous adenosine contributes to hypoxic synaptic depression in hippocampus from young and aged rats.
1. Extracellular field potentials were recorded to study the role of endogenous adenosine during hypoxia in area CA1 of rat hippocampal slices. 2. Hypoxic conditions, induced by 15 min exposure to 95% N2-5% CO2 at 32 degrees C and in high-glucose incubation medium, produced a rapid and reversible depression of evoked synaptic potentials. 3. In slices from young Sprague-Dawley rats, the hypoxia-induced synaptic depression was reduced in a concentration-dependent manner by the adenosine antagonist 8-cyclopentyltheophylline (8-CPT; 100 nM-2.0 microM). 4. Recovery of synaptic potentials after hypoxia was complete under each experimental condition. 5. Extended periods of hypoxia lasting 30 min likewise produced a rapid and near total suppression of the evoked synaptic potentials. In the presence of 8-CPT, both the population excitatory postsynaptic potential (EPSP) slope and population spike amplitude were significantly preserved throughout the hypoxic episode. 6. Neither the onset rate nor the degree of the hypoxia-induced synaptic depression were significantly different in slices from young, adult, or aged Fischer 344 rats. Reduction of the hypoxia-induced response depression by 8-CPT was also similar in all age groups. 7. These findings have further characterized the important involvement of endogenous adenosine in the potentially neuroprotective synaptic depression observed in hippocampal slices from young and aged rats during hypoxia.
Gribkoff
V K
VK
Department of Neuropharmacology, Bristol-Myers Squibb Pharmaceutical Research Institute, Wallingford, Connecticut 06492.
Bauman
L A
LA
D000241:Adenosine / Q000502:physiology*; D000375:Aging / Q000502:physiology*; D000818:Animals; D015687:Cell Hypoxia / Q000502:physiology*; D005071:Evoked Potentials / Q000502:physiology; D006624:Hippocampus / Q000502:physiology*; D066298:In Vitro Techniques; D008297:Male; D009584:Nitrogen / Q000494:pharmacology; D051381:Rats; D011916:Rats, Inbred F344; D013569:Synapses / Q000502:physiology*; D013806:Theophylline / Q000031:analogs & derivatives / Q000494:pharmacology
C053907:8-cyclopentyl-1,3-dimethylxanthine; D013806:Theophylline; D000241:Adenosine; D009584:Nitrogen