Cell loss in the cerebellum and hippocampal formation of adult rats after long-term low-protein diet.

Whereas quite a number of previous reports have shown that the developing brain is vulnerable to protein deprivation, the mature CNS is usually considered resistant to this condition. To explore this assumption the present experimental model was built on groups of 2-month-old rats fed with a low-protein diet (8% casein) for 6, 12, and 18 months and respective age-matched controls fed for the same periods with a standard laboratory chow (27% casein). The numerical density of cerebellar granule cells was estimated using three different stereological procedures (classical, unfolding, and disector). By all methods a significant cell loss was demonstrated. In the hippocampal region the numerical densities of dentate gyrus granule cells and the CA3 pyramidal cells were estimated using the unbiased disector method. A significative and progressive loss of neurons was likewise found. The occurrence of cell loss after lengthy periods of undernutrition in adulthood is thus an issue of paramount importance if extrapolation can be made to the human brain.

Effects of long-term hypothyroidism in the morphology and synaptic organization of cerebellar ectopic granule cells.

Abundant ectopic granule cells scattered in the cerebellar molecular layer have been observed in 30-day-old hypothyroid rats. Their morphological features indicate that they must be regarded as mature heterotopic cells arrested during their migration towards the granular layer. As their impoverished dendritic trees are identical to those seen in controls, it is unlikely that the lack of thyroid hormones played a major role in the deficient dendritic outgrowth. The study of 180-day-old hypothyroid rats revealed that although ectopic granule cells remained quite numerous, their number per unit surface was lesser than in the 30-day-old hypothyroid group. This finding may be related to the capacity displayed by heterotopic neurons to establish synaptic contacts with the components of the molecular layer. This was inferred by the presence of a peculiar synaptic cell investment formed by axosomatic and somatodendritic contacts in 180-day-old hypothyroid rats which shows that the surviving ectopic granule cells manage to adapt to an adverse milieu.