title: Long-term potentiation protects rat hippocampal slices from the effects of acute hypoxia.
abstract: We have previously shown that long-term potentiation (LTP) decreases the sensitivity of glutamate receptors in the rat hippocampal CA1 region to exogenously applied glutamate agonists. Since the pathophysiology of hypoxia/ischemia involves increased concentration of endogenous glutamate, we tested the hypothesis that LTP could reduce the effects of hypoxia in the hippocampal slice. The effects of LTP on hypoxia were measured by the changes in population spike potentials (PS) or field excitatory post-synaptic potentials (fepsps). Hypoxia was induced by perfusing the slice with (i) artificial CSF which had been pre-gassed with 95%N2/5% CO2; (ii) artificial CSF which had not been pre-gassed with 95% O2/5% CO2; or (iii) an oxygen-glucose deprived (OGD) medium which was similar to (ii) and in which the glucose had been replaced with sucrose. Exposure of a slice to a hypoxic medium for 1.5-3.0 min led to a decrease in the PS or fepsps; the potentials recovered to control levels within 3-5 min. Repeat exposure, 45 min later, of the same slice to the same hypoxic medium for the same duration as the first exposure caused a reduction in the potentials again; there were no significant differences between the degree of reduction caused by the first or second exposure for all three types of hypoxic media (P>0.05; paired t-test). In some of the slices, two episodes of LTP were induced 25 and 35 min after the first hypoxic exposure; this caused inhibition of reduction in potentials caused by the second hypoxic insult which was given at 45 min after the first; the differences in reduction in potentials were highly significant for all the hypoxic media used (P<0.01; paired t-test). The neuroprotective effects of LTP were not prevented by cyclothiazide or inhibitors of NO synthetase compounds that have been shown to be effective in blocking the effects of LTP on the actions of exogenously applied AMPA and NMDA, respectively. The neuroprotective effects of LTP were similar to those of propentofylline, a known neuroprotective compound. We conclude that LTP causes an appreciable protection of hippocampal slices to various models of acute hypoxia. This phenomenon does not appear to involve desensitisation of AMPA receptors or mediation by NO, but may account for the recognised inverse relationship between educational attainment and the development of dementia.
authors: Department of Preclinical Sciences, University of the West Indies, St. Augustine Campus, St. Augustine, Trinidad and Tobago.
authors: F F
authors: FF
authors: Youssef
authors: J I
authors: JI
authors: Addae
authors: A
authors: A
authors: McRae
authors: T W
authors: TW
authors: Stone
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000208:Acute Disease; D000818:Animals; D001581:Benzothiadiazines / Q000494:pharmacology; D002245:Carbon Dioxide / Q000494:pharmacology; D015687:Cell Hypoxia; D016895:Culture Media, Serum-Free / Q000494:pharmacology; D004558:Electric Stimulation; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D005947:Glucose / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*; D020925:Hypoxia-Ischemia, Brain / Q000473:pathology / Q000503:physiopathology*; D017774:Long-Term Potentiation / Q000187:drug effects; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology; D019335:Nitroarginine / Q000494:pharmacology; D010100:Oxygen / Q000494:pharmacology; D017966:Pyramidal Cells / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000187:drug effects; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects; D013395:Sucrose / Q000494:pharmacology; D014970:Xanthines / Q000494:pharmacology
chemical_list: D001581:Benzothiadiazines; D016895:Culture Media, Serum-Free; D018696:Neuroprotective Agents; D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; D014970:Xanthines; D002245:Carbon Dioxide; D019335:Nitroarginine; D013395:Sucrose; C032114:propentofylline; D005947:Glucose; C004639:cyclothiazide; D010100:Oxygen