The new pyridoindole antioxidant SMe1EC2 and its intervention in hypoxia/hypoglycemia-induced impairment of long-term potentiation in rat hippocampus

Gáspárová, Zdenka; Šnirc, Vladimír; Štolc, Svorad

doi:10.2478/v10102-011-0011-0

Abstract

Previously, the pyridoindole SMe1EC2 was proved to inhibit lipoperoxidation and carbonylation of proteins in rat brain cortex in the system Fe²⁺/ascorbate and improvement of resistance of the rat hippocampus was reported against ischemic conditions in vitro (hypoxia/hypoglycemia) expressed by the enhanced neuronal response recovery in reoxygenation. The hippocampus fulfils many of the criteria for a neuronal correlate of learning and memory. Recently, an impairment of hippocampal long-term potentiation (LTP) was reported under oxidative stress. Different therapies, including antioxidants, have been studied intensively concerning the impairment of neuronal plasticity. In this study marked reduction of LTP, elicited by a single burst (100 Hz, 1s) in the CA3-CA1 area of rat hippocampal slices, was shown due to transient hypoxia/hypoglycemia compared to control slices. On the basis of previously reported antioxidant and neuroprotective effects of SMe1EC2, its effect on loss of LTP in the hippocampus due to ischemic conditions was studied in vitro. The pyridoindole tested improved hypoxia/hypoglycemia-induced reduction of LTP compared to untreated hypoxic slices. An opposite effect of SMe1EC2 on LTP induction was found in control slices. The mechanism of SMe1EC2 action on LTP in ischemic conditions has been suggested to differ from the mechanism of its effect in "normoxia" and may be due to different redox status in control and ischemic brain tissue. The manifested LTP-protective effect of SMe1EC2 observed in the rat hippocampus exposed to ischemia in vitro may find exploitation in therapy associated with injured neuronal plasticity in some conditions, including ischemia, trauma and aging in man.

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The new pyridoindole antioxidant SMe1EC2 and its intervention in hypoxia/hypoglycemia-induced impairment of long-term potentiation in rat hippocampus

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