Lead, GABA, and seizures: Effects of subencephalopathic lead exposure on seizure sensitivity and GABAergic function

Ellen K. Silbergeld, Leonard P. Miller, Shawn Kennedy, Nancy Eng

Research output: Contribution to journalArticlepeer-review

Abstract

Seizures have been described as the endpoint of lead (Pb) intoxication in both humans and animals. Alterations in blood-brain barrier integrity may underlie some cases of Pb-induced seizures, but seizures can also occur in the absence of changes in blood-brain barrier. Exposure of rats to two levels of Pb below those producing overt encephalopathy sensitizes them to the behavioral effects of the convulsant agents picrotoxin, isoniazid, mercaptopropionic acid, and strychnine, but not pentylenetetrazol (PTZ). Pb exposure affects several aspects of regional GABAergic function: GABA-transaminase (GABA-T) and glutamic acid decarboxylase (GAD) activities, GABA levels, and apparent rate of GABA synthesis. The results indicated that Pb increased GAD activity, decreased GABA-T activity, and increased the apparent rate of GABA synthesis. However, these changes were not observed consistently in all regions studied. Pb exposure also inhibited the uptake and release (unstimulated and K-stimulated) of [14C]GABA; this effect was observed in both Pb treatment groups and in all brain regions except the cerebellum. The results support an hypothesis of a neurochemical basis for Pb-induced seizures, involving inhibition of GABAergic neurotransmission.

Original languageEnglish (US)
Pages (from-to)371-382
Number of pages12
JournalEnvironmental research
Volume19
Issue number2
DOIs
StatePublished - Aug 1979
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Environmental Science(all)

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