Comparative study of the influence of Thy1 deficiency and dietary iron deficiency on dopaminergic profiles in the mouse striatum

Abstract

Thy-1, a glycosyl-phosphatidylinositol (GPI)-linked integral membrane protein, may play a role in stabilizing synapses. Thy1 was identified in a gene expression analysis as iron responsive, and subsequent cell culture and animal models of iron deficiency expanded this finding to the protein. The importance of Thy1 in influencing neurotransmitter feedback mechanisms led to this study to determine the relative effects of Thy1 deficiency and dietary iron deficiency on the dopaminergic system in the mouse striatum. The model for this analysis was the Thy1 null mutant mouse in the presence or absence of dietary iron deficiency. The results revealed significant differences in dopaminergic profiles associated with Thy1 and iron deficiency and also a sex effect. For example, both iron deficiency and the absence of Thy1 are associated with increased dopamine in both sexes, but the dopamine transporter is increased in these experimental groups only in female mice. In male mice, the increase in dopamine transporter is found only in the Thy1 null mutants. Increases in vesicular monoamine transporter and phosphorylated tyrosine hydroxlyase are found only in iron-deficient mice. In contrast decreased release of dopamine from synaptosomes is found only in the Thy1 null mutant animals. In general, these results indicate that a loss of Thy1 can influence the dopaminergic profile in the striatum. Furthermore, the results reveal consistent differences in the dopaminergic profile in Thy1 knockout mice compared with iron-deficient mice, indicating that the effects of iron deficiency are not due only to a change in Thy1 expression.