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.
ASJC Scopus subject areas
- General Environmental Science