Effects of Mild Hyperthyroidism on Levels of Amino Acids in the Developing Lurcher Cerebellum

Abstract

This study examines the question of whether intrinsically defective mutant Lurcher Purkinje cells, which degenerate during postnatal weeks two to five, followed by later loss of granule cells are competent to respond to neonatal hyperthyroidism, which is known to cause premature differentiation of Purkinje cells and an acceleration of the peak of proliferation in granule cells in normal rodent cerebellum. Both total amounts and concentrations (per mg wet weight) of Tau, Glu, Asp and GABA were assayed as markers of cell function in Lurcher and wild-type mice made very mildly hyperthyroid by feeding nursing dams high-thyroxine food. Tau, which is present in relatively high concentrations in Purkinje cells, was affected by hyperthyroid treatment in the Lurcher in a manner that is most consistent with an acceleration of the degenerative process in Purkinje cells. The acidic amino acids Glu and Asp show later changes and response to hormone which seem to be a reaction to the Purkinje cell pattern, probably in the granule cells. We conclude that the Lurcher cerebellum is particularly sensitive to thyroid hormone, and that it responds to low levels of hyperthyroidism in a distinct way.