Non-phosphorylated and phosphorylated neurofilaments in the cerebellum of the rat: an immunocytochemical study using monoclonal antibodies. Development in normal and thyroid-deficient animals.
The immunocytochemical staining patterns of two monoclonal antibodies specifically directed against non-phosphorylated and phosphorylated neurofilaments were studied during development of cerebellum in normal and thyroid-deficient rats. In normal animals, non-phosphorylated neurofilaments first appeared in Purkinje cell cytoplasm, then in dendritic tree and axon. They were also observed in basket cell axons running in the lower parts of the molecular layer and thereafter around the initial segment of Purkinje cell axons. Thyroid deficiency markedly retarded the appearance of these non-phosphorylated neurofilaments in Purkinje cells. More strikingly, the labelling in basket cell axons never appeared. In normal animals, phosphorylated neurofilaments were localized only in axons. They were first restricted to Purkinje cell axons and then appeared in basket cell axons. In thyroid-deficient rats, a transient weak labelling was observed in the cytoplasm of the Purkinje cells. Moreover, the characteristic arrangement of basket cell axons around the Purkinje cell body and proximal axon was never observed. Hypothyroidism thus retards the appearance of neurofilaments in Purkinje and basket cells and transiently disturbs their phosphorylation state. It also disorganized the basket cell morphogenesis and consequently the major inhibitory pathway of the cerebellar cortex. This last effect is only poorly corrected when the animals are allowed to return to an euthyroid state after one month of postnatal antithyroid treatment.
D000818:Animals; D002525:Cerebellar Cortex / Q000378:metabolism; D002529:Cerebellar Nuclei / Q000378:metabolism; D002531:Cerebellum / Q000254:growth & development / Q000378:metabolism*; D003599:Cytoskeleton / Q000378:metabolism*; D007037:Hypothyroidism / Q000378:metabolism* / Q000503:physiopathology; D007124:Immunoenzyme Techniques; D007382:Intermediate Filaments / Q000378:metabolism*; D010766:Phosphorylation; D051381:Rats; D011919:Rats, Inbred Strains