Hypothyroidism cerebellum

The most significant of the abnormalities observed in a hypothyroid brain is a hypoplastic neuropile, i.e., a marked reduction in the number of connections between neurons [102], This has been observed both in the cerebrum and the cerebellum. For instance a permanent and dramatic reduction in the arborization of the dendritic tree of the Purkinje cell is observed in the hypothyroid cerebellum [103]. The length of the primary dendritic trunk is increased and a deficit in the number, density and branching of the dendritic spines is noticed. In contrast neonatal hyperthyroidism accelerates development of spines. Similar findings have been reported for the cerebrum, i.e., reduction in length and branching of pyramidal neurons, of the density of axonal terminals and of the number of spines [102],... 

Clos, J. and Legrand, C. (1990) An interaction between thyroid hormone and nerve growth factor promotes the development of hippocampus, olfactory bulbs and cerebellum a comparative biochemical study of normal and hypothyroid rats. Growth Factors 3 205-220. 

Bernal (2005) reviewed the morphological aspects in the brain of the hypothyroid rat and found (1) altered cell migration, particularly in the cerebellum and cerebral cortex (2) increments in cell density, caused by a reduction in the neuropil (3) markedly reduced dendritic arborization in the Purkinje cells of the cerebellum, and decreased and altered distribution of the pyramidal dendritic spines in the cortex layer V and finally (4) delayed myelination and poor myelin deposit in the white matter and fewer myelinated axons. This study further showed that hypothyroidism produces changes in the colossally projecting neurons, which may be due to the maintenance of juvenile patterns of projections. In addition, a recent report (Lavado-Autric et al., 2003) indicates that focusing on maternal hypothyroidism can produce migration defects in the fetal cortex, when... 

The role of TH is the coordination of seemingly unrelated maturation processes. TH can influence these processes only temporarily during overlapping windows of development with regional specificity. Studies of clinical thyroid disorders and experimental models show that the timing of TH deficiency produces different effects, as illustrated in Figure 108.3 (Zoeller and Rovet, 2004). Furthermore, it is important to confirm the precise time when the THs critical point of activity in brain development occurs, such as the rate of cell division or cell death at specific times in the development of the cerebellum, in order to prevent the irreversible neurological deficits of hypothyroidism in childhood. 

Rabie, A., Favre, C., Clavel, M.C., and Legrand, J., 1979a, Sequential effects of thyroxine on the developing cerebellum of rats made hypothyroid by propylthiouracil, Brain Res.. 161 469. 

A similar conclusion applies to the cerebellum of a hypothyroid rat (Fig.3) but at day 15 postnatal the maturation process is delayed and severed abnomalities are observed (Brion et al., unpublished results). For instance the es ression of Tau in the paredlel fibers resembles at day 15 that observed at day 10 in the euthyroid control. Major abnormalities were also seen at the level of the Purkinje cells. Labeling with an anti-MAP2 antibody showed that 1) as previously described by... 

Figure 3. IniniMX)histoch0ndcal staining of 14 day old euthyroid ih,B) and hypothyroid (CrD) rat cerebellum with anti-Tau (A,C) and anti-MM>2 (B D) antibodies. Purkinje cell body (P) and their dendritic tree (D). Parallel fiber axons (A).

Animal models in the marmoset and the sheep have been developed to study the effect of severe iodine deficiency on brain development. Both these models are characterised by the production of severe maternal and fetal hypothyroidism which is associated with effects on the maturation of the cerebral cortex and cerebellum. There was a reduced brain weight with a reduced number of cells as indicated by reduced DNA, a greater density of cells in the cerebral cortex and reduced cell acquisition in the cerebellum. 

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