Neuronal maturation in the normal and hypothyroid rat cerebellar cortex studied with monoclonal antibody MIT-23.
By immunocytochemistry we have studied the expression of the mitochondria-associated polypeptide MIT-23 during the postnatal development of the normal and hypothyroid rat cerebellar cortex, in afferent fibers, and also in neurons of the cerebellar nuclei. The glial cells are never immunoreactive. In all neurons of the cerebellar cortex, MIT-23 expression always occurs after the final mitosis and migration are complete, and persists throughout adult life. Almost all MIT-23 expression begins postnatally. A few Purkinje cells are already immunoreactive at birth and the rest begin expression during the following two days. Immunoreactive Golgi and granule cells are found from postnatal day 4 (P4), basket cells from P10, and stellate cells from P16. Purkinje cells from different anteroposterior regions of the vermis express different levels of MIT-23 with higher staining intensities in lobules I to IV. These differences appear early in development and are retained in the adult. MIT-23 expression in the hypothyroid cerebellar cortex differs from that in control animals only in minor ways. However, sections immunoperoxidase-stained with anti-MIT-23 antibody reveal that, in addition to previously reported alterations in cerebellar development due to a shortage of thyroid hormones, Purkinje cell axonal development is slowed down in the hypothyroid condition, and occasional Purkinje cells in normal and especially in hypothyroid animals have their somata and or dendrites in ectopic locations. Analysis of these cells reveals a preferential direction of dendritic trunk growth in the direction of the molecular layer. Furthermore, secondary branching of ectopic dendrites is confined exclusively to the developing molecular layer, as in normal Purkinje cells, thus suggesting that neither the mature nor immature granule cell environment is sufficient to sustain normal dendritic development.
Gravel
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C
Hawkes
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R
D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism*; D002465:Cell Movement; D002525:Cerebellar Cortex / Q000254:growth & development* / Q000378:metabolism; D007037:Hypothyroidism / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D007124:Immunoenzyme Techniques; D011689:Purkinje Cells / Q000378:metabolism / Q000473:pathology; D051381:Rats
D000911:Antibodies, Monoclonal