Iron concentration reduced in ventral pallidum, globus pallidus, and substantia nigra by GABA-transaminase inhibitor, gamma-vinyl GABA

Abstract

Recent histochemical studies indicate that there is considerable overlap of brain areas accumulating iron in oligodendrocytes with those in which GABA neurons terminate. The ventral pallidum, globus pallidus, substantia nigra and cerebellar nuclei are iron-rich areas, receive GABA-containing efferents, and have high concentrations of gamma-aminobutyric acid (GABA) and glutamic acid decar☐ylase (GAD). The present study examines the efect of disruption of the metabolism of GABA on the accumulation of iron in GABAergic projection sites. Gamma-vinyl GABA, an enzyme activated inhibitor of GABA-transaminase, was injected unilaterally into the globus pallidus and adjacent striatum or into the substantia nigra of the rat brain. Additional animals received unilateral injections of saline into the same areas or an electrocoagulation lesion of the globus pallidus and surrounding striatum. Two days after injection or lesion all animals were perfused and 40 μm sections of the brain were processed with the Perls' + diaminobenzidine (DAB) histochemical method for iron. The intensity of iron stain was measured with densitometry. Gamma-vinyl GABA injection into the striatum/pallidum resulted in a significant reduction in iron concentration in the ipsilateral ventral pallidum, globus pallidus and substantia nigra. Gamma-vinyl GABA injected into the substantia nigra reduced iron in the injection site. This study provides evidence that the presence of iron in the brain is related to the utilization of GABA.