Free radicals accelerate the decay of long-term potentiation in field CA1 of guinea-pig hippocampus.

Free radicals have been implicated in a number of pathological conditions. To evaluate the neurophysiological consequences of free radical exposure, slices of hippocampus isolated from guinea-pigs were exposed to hydrogen peroxide which reacts with tissue iron to generate hydroxyl free radicals. Long-term potentiation, a sustained increase in synaptic responses, was elicited in field CA1 by high frequency stimulation of an afferent pathway.

MPP+-induced pathophysiology demonstrates advantages of neurotoxicology studies in brain slices.

Since MPTP and its metabolite MPP+ produce nigrostriatal lesions and symptoms similar to Parkinson's disease, recent studies have aimed toward defining their selectivity and neurotoxic mechanisms. In mitochondria in vitro, MPP+ blocked electron transport and decreased oxygen consumption. However, these effects were not selective to striatal mitochondria or even to mitochondria from brain, they required concentrations of MPP+ much greater than those found in vivo, and physiological actions could not be related to intramitochondrial changes.

MPP+-induced increases in extracellular potassium ion activity in rat striatal slices suggest that consequences of MPP+ neurotoxicity are spread beyond dopaminergic terminals.

MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) produces symptoms similar to idiopathic Parkinson's disease in primates. A metabolite of MPTP, MPP+ (1-methyl-4-phenylpyridinium), is actively accumulated by dopaminergic (DA) terminals and selectively destroys nigrostriatal DA neurons. The mechanism of this effect remains unknown but reports that MPP+ inhibits electron transport in isolated mitochondria and increases oxidation of cytochrome b in striatal slices suggest that depression of ATP production is involved.

1-Methyl-4-phenylpyridinium (MPP+) increases oxidation of cytochrome-b in rat striatal slices.

Effects of 1-methyl-4-phenylpyridinium, (the active metabolite of the neurotoxin, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine), on reduction/oxidation activity of mitochondrial cytochromes were studied in rat striatal slices using scanning spectrophotometry. The objective was to test the hypothesis that the neurotoxin alters electron transport in the mitochondrial respiratory chain. Incubation of rat striatal slices with MPP+ (1 microM) produced a time-dependent oxidation of Cytochrome-b in a manner consistent with the concept of a block in electron transport in the intramitochondrial respiratory chain between nicotinamide adenine dinucleotide (NAD) and Cytochrome-b.