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Melatonin protects primary cultures of cerebellar granule neurons from kainate but not from N-methyl-D-aspartate excitotoxicity.

Abstract：

:the antiexcitotoxic efficacy of melatonin, a putative endogenous hydroxyl radical scavenger, was studied in primary cultures of rat cerebellar granule neurons. Excitotoxicity was induced in 7- to 9-day-old cultures by an exposure to glutamate (15 min in the absence of magnesium) or to glutamate receptor agonists, kainate (30 min), and N-methyl-D-aspartate (60 min in the absence of magnesium). Thereafter, cultures were returned to the culture-conditioned medium for 18 h at the end of which time viability was assessed by quantitative staining with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide. Cotreatment with melatonin (500 microM) protected the neurons completely from the toxicity of kainate (up to 1 mM) and shifted the ED50 for glutamate from 55 +/- 2.6 to 97 +/- 3.6 microM. Melatonin cotreatment was ineffective in protecting the neurons from N-methyl-D-aspartate toxicity. When melatonin was added to the cultures only before or after kainate treatment, there was no resultant protection from kainate toxicity. The neuroprotective effect of melatonin does not appear to be related to the direct action of melatonin on ionotropic glutamate receptors. That is, the kainate-stimulated inward currents measured by a patch-clamp technique in voltage clamped neurons and the kainate-stimulated increase in free cytosolic calcium measured at the single-cell level using digital imaging fluorescent microscopy with fura-2 were not affected by melatonin. Moreover, the binding of [3H]glutamate to rat cerebellar membranes was not competed off by melatonin. Further studies are needed to evaluate the pharmacologic relevance of the neuroprotective action of melatonin.

journal_name

Exp Neurol

journal_title

Experimental neurology

authors

Giusti P,Gusella M,Lipartiti M,Milani D,Zhu W,Vicini S,Manev H

doi

10.1016/0014-4886(95)90005-5

subject

Has Abstract

pub_date

1995-01-01 00:00:00

pages

39-46

issue

1

eissn

0014-4886

issn

1090-2430

journal_volume

131

pub_type

杂志文章

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