Thyroid hormone modulates the expression of a neurofilament antigen in the cerebellar cortex: premature induction and overexpression by basket cells in hyperthyroidism and a critical period for the correction of hypothyroidism.
Neurofilament expression by basket cells of the cerebellar cortex is suppressed in hypothyroidism. By using a monoclonal antibody (mabN210) that selectively recognizes an epitope associated with the 210-kDa neurofilament subunit, we have explored the relationship between thyroid hormone levels and basket cell maturation. In animals rendered hypothyroid by inclusion of propylthiouracil in the maternal drinking water from embryo age E17, there is a complete absence of mabN210 immunoreactivity in the basket cell axons, while the other immunoreactive axons in the cerebellar cortex, primarily Purkinje cell axons and mossy fibers, are apparently unaffected. This deficit can be corrected by treatment with thyroid hormone but there seems to be a critical period for full recovery, for animals treated from birth recover normally whereas there is a gradual diminution in the efficacy of treatment the later it begins. Thyroid hormone therapy begun after postnatal day 30 (P30) leads only to very minor recovery. By contrast, animals on a hyperthyroid regime show premature mabN210-antigen induction in the basket cells and supranormal levels of expression at P25, despite the severe reduction in the number of basket cell somata. This suggests either abnormal compensatory sprouting of axon collaterals by the remaining basket cells or the occurrence, during normal cerebellar corticogenesis, of competition between basket cell axons for a limited number of Purkinje cell targets followed by the elimination of the excess collaterals.
D000818:Animals; D000941:Antigens / Q000032:analysis; D002525:Cerebellar Cortex / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D000939:Epitopes / Q000032:analysis; D006980:Hyperthyroidism / Q000378:metabolism* / Q000473:pathology; D007037:Hypothyroidism / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D007381:Intermediate Filament Proteins / Q000096:biosynthesis* / Q000276:immunology; D051381:Rats; D011919:Rats, Inbred Strains; D013974:Thyroxine / Q000494:pharmacology* / Q000627:therapeutic use
D000941:Antigens; D000939:Epitopes; D007381:Intermediate Filament Proteins; D013974:Thyroxine