Effects of lead in vivo and in vitro on GABAergic neurochemistry

Ellen Silbergeld, R. E. Hruska, L. P. Miller, N. Eng

Research output: Contribution to journalArticle

Abstract

Alterations in aspects of neurotransmission utilizing γ-aminobutyric acid (GABA) are associated with in vivo exposure of rats to lead at doses that do not produce convulsions, but sensitize animals to convulsant agents. These effects are observed regionally and include: decreased GABA levels in cerebellum; increased activity of glutamate decarboxylase (GAD) in caudate; and decreased GABA release (both resting and K+-stimulated) in cortex, caudate, cerebellum, and substantia nigra. Sodium-dependent uptake of GABA by synaptosomes of cerebellum, substantia nigra and caudate was also affected: in the regions, affinity (Km) was increased and maximal velocity (Vmax) was reduced. Sodium-independent binding of GABA to synaptic membranes was increased in cerebellum, but was observed only when tissue was Tritonized and prepared without freezing and washing. No effects on GAD or on GABA uptake, release, or binding were observed when lead was added to brain tissue in vitro in concentration as high as 100μM. The results suggest that lead may produce chronic inhibition of presynaptic GABAergic function, notably in the cerebellum, which is associated with supersensitivity of postsynaptic GABA receptors. Failure of lead to affect GABAergic function in vitro may indicate that these effects are secondary to another neurotoxic action of lead in the CNS or are consequent to a nonneuronal metabolic action of lead.

Original languageEnglish (US)
Pages (from-to)1712-1718
Number of pages7
JournalJournal of Neurochemistry
Volume34
Issue number6
StatePublished - 1980
Externally publishedYes

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Neurochemistry
gamma-Aminobutyric Acid
Cerebellum
Glutamate Decarboxylase
Substantia Nigra
Sodium
Tissue
Aminobutyrates
Convulsants
Synaptic Membranes
GABA Receptors
Synaptosomes
Washing
Freezing
Synaptic Transmission
Lead
In Vitro Techniques
Rats
Brain
Animals

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

Cite this

Silbergeld, E., Hruska, R. E., Miller, L. P., & Eng, N. (1980). Effects of lead in vivo and in vitro on GABAergic neurochemistry. Journal of Neurochemistry, 34(6), 1712-1718.

Effects of lead in vivo and in vitro on GABAergic neurochemistry. / Silbergeld, Ellen; Hruska, R. E.; Miller, L. P.; Eng, N.

In: Journal of Neurochemistry, Vol. 34, No. 6, 1980, p. 1712-1718.

Research output: Contribution to journalArticle

Silbergeld, E, Hruska, RE, Miller, LP & Eng, N 1980, 'Effects of lead in vivo and in vitro on GABAergic neurochemistry', Journal of Neurochemistry, vol. 34, no. 6, pp. 1712-1718.
Silbergeld, Ellen ; Hruska, R. E. ; Miller, L. P. ; Eng, N. / Effects of lead in vivo and in vitro on GABAergic neurochemistry. In: Journal of Neurochemistry. 1980 ; Vol. 34, No. 6. pp. 1712-1718.
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