Time scale and extent of neuronal and synaptic loss in the hippocampal formation of malnourished adult rats.

We have demonstrated that a prolonged low-protein diet induces neuronal and synaptic loss in the hippocampal formation of the adult rat. Because 6 months of protein deprivation was the shortest period analyzed in the previous investigations, in the present study we have evaluated the length of the treatment period necessary to induce significant changes in the numbers of neurons and synapses. Groups of 2-month-old rats were analyzed: (1) and (2) malnourished for 1 and 3 months with a low-protein diet (8% casein): (3) and (4) age-matched control rats fed with a standard diet. Stereological methods were employed to estimate the total number of granule, hilar, CA3 and CA1 pyramidal cells and the volume of the respective cell layers, the volume of the mossy fiber system and the number and related quantitative features of mossy fiber-CA3 synapses. No differences in the number of cells or synapses were found between 1-month malnourished rats and the respective controls. However, in rats treated for 3 months the total number of granule cells. CA3 and CA1 pyramidal cells was reduced, as was the total number of synapses. These findings indicate that the changes induced by protein deprivation progressively increase during the early phases of treatment and that they are already evident after 3 months of protein deprivation.