A molecular form of memory protects the brain from the effects of acute hypoxia [abstract]

ABSTRACT

Long-term potentiation (LTP) is a molecular engram of memory. Previous work has demonstrated that LTP decreases the sensitivity of glutamate receptors in the rat hippocampus. Glutamate has beem implicated in the pathogenesis of hypoxic/ischaemic damage. We therefore tested the hypothesis that LTP could reduce the effects of LTP on hypoxia in the rat hippocampus. The effects of LTP on hypoxia were measured by the changes in the extracellular potentials recorded from the hippocampal slice. Hypoxia was induced by perfusing the slice with artificial cerebrospinal fluid that contained varying concentrations of oxygen. Each slice was initially exposed to the hypoxic medium for 1.5-3.0 minutes. This led to a decrease in the potentials, which recovered to control levels within 5 minutes. Repeat exposure to the same hypoxic medium for the same duration as the first, also caused a reduction in the potentials. There was no significant difference between the degree of reduction caused by the first or second exposure for all types of hypoxic media tested (p >0.05; paired t test). In some slices, LTP was induced after the first hypoxic exposure. LTP brought about an inhibition of the reduction in potentials caused by the second hypoxic insult; the differences in reducation 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 (an inhibitor of AMPA receptor desensitization) or NOS inhibitors (antagonists of intracellular nitric oxide production). These compounds 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 that of propentofylline, a known neuroprotective compound. We conclude that LTP causes an appreciable protection of the hippocampus slices to in-vitro models of acute hypoxia. There have been reports that there is a possible inverse relationship between educational attainment and the development of dementia and the results of our study may have a role to play in this relationship. (AU)