Lead, GABA, and seizures: effects of subencephalopathic lead exposure on seizure sensitivity and GABAergic function. [Rats]

Journal Article · Wed Aug 01 04:00:00 EDT 1979 · Environ. Res.; (United States)

DOI:https://doi.org/10.1016/0013-9351(79)90062-8· OSTI ID:5406935

Silbergeld, E K; Miller, L P; Kennedy, S; Eng, N

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 pentylenetetrazole (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 (/sup 14/C)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.

• Research Organization: National Institutes of Health, Bethesda, MD
• OSTI ID: 5406935
• Journal Information: Environ. Res.; (United States), Journal Name: Environ. Res.; (United States) Vol. 19:2; ISSN ENVRA
• Country of Publication: United States
• Language: English

Related Subjects

550100 -- Behavioral Biology
550201 -- Biochemistry-- Tracer Techniques
560305* -- Chemicals Metabolism & Toxicology-- Vertebrates-- (-1987)
59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ALKALOIDS
AMINO ACIDS
AMINOBUTYRIC ACID
AMINOTRANSFERASES
ANIMALS
AZOLES
BEHAVIOR
BIOLOGICAL EFFECTS
BLOOD-BRAIN BARRIER
BODY
BRAIN
CARBON 14 COMPOUNDS
CARBOXYLIC ACIDS
CATALYSIS
CENTRAL NERVOUS SYSTEM
DATA
DATA FORMS
DECARBOXYLASE
DISEASES
DOSE-RESPONSE RELATIONSHIPS
DRUGS
ELEMENTS
ENZYMES
EXPERIMENTAL DATA
HETEROCYCLIC COMPOUNDS
HYDRAZIDES
INDOLES
INFORMATION
ISOLATED VALUES
ISONIAZID
ISOTOPE APPLICATIONS
LABELLED COMPOUNDS
LEAD
LYASES
MAMMALS
METABOLISM
METALS
NERVOUS SYSTEM
NERVOUS SYSTEM DISEASES
NUMERICAL DATA
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANIC SULFUR COMPOUNDS
ORGANS
PYRROLES
QUANTITY RATIO
RATS
RODENTS
STRYCHNINE
THIOLS
TOXICITY
TRACER TECHNIQUES
TRANSFERASES
VERTEBRATES