Thyroid hormone effects on neuronal differentiation during brain development.

Neurite outgrowth and acquisition of neuronal polarity depend on microtubule assembly and this process is impaired when hypothyroidism is established at late fetal stages in the rat. Taking in account these observations the effects of thyroid hormone deficiency in the developing cerebellum were studied with probes for different tubulin isoforms and for two microtubule-associated proteins, tau and MAP2, which are specific for the axons and the dendrites, respectively. The results showed that thyroid hormone deficiency: 1) desynchronizes the spatio-temporal program of axonal and dendritic differentiation in the cerebellum. 2) Modifies the developmental pattern of expression of various tubulin isoforms. 3) Delays replacement of the immature tau variants by the mature forms. The adult variants of tau proteins specify adult and stable axons whereas the juvenile forms are expressed when axons are growing actively. According to these criteria the hypothyroid brain remains immature at stages when proper connectivity is normally established. Thyroid hormone appears therefore as an epigenic signal that synchronizes axonal and dendritic outgrowth, two major parameters of the construction of the neuronal network.