Brain neuronal chromatin responses in acute soman intoxicated rats

L. J. Martin, J. A. Doebler, T. J. Wall, T. M. Shih, A. Anthony

Research output: Contribution to journalArticle

Abstract

Male Sprague-Dawley rats (200 g) were injected subcutaneously with soman, a potent neuronal acetylcholinesterase (AChE) inhibitor, at doses of 0.5, 0.8 and 1.0 LD50 (1 LD50=135 μg/kg) before decapitation at 1 and 24 h post-exposure. Correlative data were obtained on the severity of brain AChE inactivation and physicochemical changes in nuclear chromatin of cerebrocortical (layer V) and striatal neurons using Feulgen-DNA (F-DNA) cytophotometry and ocular filar micrometry. Decreased lability of neurons to F-DNA acid hydrolysis (reduced F-DNA yield), nuclear shrinkage and chromatin aggregation (decreased chromophore area) were used as indices of suppression of genomic template activity; conversely, increases in F-DNA yield and chromophore area signify enhanced neuroexcitation. At 1 hr post-soman there was a dose-dependent inactivation of AChE with a moderate increase in chromatin activation, i.e., nuclear hypertrophy and chromatin dispersion. At 24 hr post-soman there was a partial restoration of AChE activity, notably in striatal neurons, with a suppression in chromatin template activity. These data indicate that actions of soman on neuronal functioning are time-dependent. The absence of any dose-related neuronal chromatin changes may signify existence of non-cholinergic mediated events.

Original languageEnglish (US)
Pages (from-to)1203-1215
Number of pages13
JournalNeurochemical Research
Volume11
Issue number8
DOIs
StatePublished - Aug 1 1986
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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