Behavioral effects of protein deprivation and rehabilitation in adult rats: relevance to morphological alterations in the hippocampal formation

In the present study we have analyzed the behavioral and neuroanatomical effects of protein deprivation in adult rats. Starting at 2 months of age, animals were maintained on 8%-casein diet either for 8 months (malnourished group), or for 6 months followed by a 2-month period of nutritional rehabilitation (17%-protein diet, rehabilitated group). Malnourished rats exhibited reduced emotional reactivity and impaired habituation in the open field. In a water maze, these animals did not differ from controls during training, but showed retention deficits on the probe trial. However, working memory, sensorimotor abilities and passive avoidance behavior were not significantly impaired in malnourished rats. The performance of rehabilitated group was similar to that of the control group throughout behavioral testing. Postmortem morphological analysis revealed that the total number of neurons in the granular layer of the dentate gyrus, and in CA3 and CA1 hippocampal fields was reduced in protein-deprived and rehabilitated rats relative to controls. In addition, it was found that protein deprivation caused a 30% loss of synapses established between mossy fibers and dendrites of CA3 pyramidal cells, whereas nutritional rehabilitation resulted in a reversal of this effect. These results show that prolonged malnutrition in adult rats produces marked loss of hippocampal neurons and synapses accompanied by substantial impairments of hippocampal-dependent behaviors. The fact that nutritional rehabilitation results in restoration of the total number of hippocampal synapses and parallel amelioration of the behavioral impairments suggests that the mature CNS possesses a remarkable potential for structural and functional recovery from the damage induced by this type of dietary insult.