The Effects of Dopamine and Estrogen upon Cortical Parvalbumin Expression

Abstract

Abstract : Estrogen plays a protective role in several neurologic disorders known to involve alterations in both the dopamine system and (gamma amino butyric acid containing) GABAergic neurons that contain parvalbumin. Two studies were conducted to identify the effects of estrogen and dopamine upon cortical parvalbumin expression. In the first study, organotypic slice cultures of the frontal cortex were prepared from male rats (postnatal age 2/3) and maintained for 14 days in serum-enriched medium or media containing either: dopamine, estrogen, or a combination of the two. In control slices, parvalbumin immunoreactive neurons were primarily clustered near cortical layer V. All treatment conditions increased the distribution of parvalbumin labeled neurons in layer VI and enhanced the maturation of dendritic measures of labeled neurons in the deep layers (V-VI). Both estrogen and the combination treatment induced similar alterations in the superficial cortical layers, as well. In the second study, gonadectomy (male rats, postnatal age 2) induced long lasting decreased in the density of parvalbumin immunoreactive neurons throughout all cortical layers. Estrogen replacement restored parvalbumin expression to control levels in the superficial cortical layers, only. Gonadectomy also increased dopaminergic neuron density in the substantia nigra, compacta and tyrosine hydroxylase fiber length in the cortex at 33 days postnatal. Estrogen replacement returned dopaminergic neuron density, but not cortical fiber length, to control levels. Neonatal 6-hydroxy dopamine (6-OHDA) lesions produced results in the cortex that were similar to those induced by gonadectomy, regardless of the loss in dopaminergic neurons. Taken together, these findings indicate that estrogen alters cortical parvalbumin expression and cortical and subcortical dopaminergic systems.