Effects of Lead In Vivo and In Vitro on GABAergic Neurochemistry

Ellen K. Silbergeld, Robert E. Hruska, Leonard P. Miller, Nancy Eng

Research output: Contribution to journalArticlepeer-review

Abstract

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 these 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 concentrations as high as 100 μM. 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
DOIs
StatePublished - Jun 1980
Externally publishedYes

Keywords

  • Glutamate decarboxylase
  • Lead
  • γ‐Aminobutyric acid

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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