Hemisphere- and subfield-specific effects of prenatal protein malnutrition on neuronal numbers in the hippocampal formation of the adult rat

Malnutrition is a global health problem that affects an estimated 840 million people worldwide, approximately 150 million of whom are below 5 years of age. Adults who suffered malnutrition during early life are developmentally delayed in many physical and cognitive measures and can have permanent cognitive deficits. Previous studies of the effects of prenatal protein malnutrition in a rat model of the kwashiorkor form of human malnutrition have demonstrated that the structure and function of the hippocampus is particularly vulnerable to this insult.; The effects of prenatal protein malnutrition on the number of neurons in the hippocampal formation of the adult rat were investigated using design-based stereological methods. Total neuron number in the hilus of the dentate gyrus and the principal cell layers of the CA3/2 subfield, the CAI subfield, and the subiculum were estimated using the optical fractionator method. Volumes of these layers were estimated using the Cavalieri method. To investigate the effect of the insult on the inhibitory system, numbers of parvalbumin-immunoreactive interneurons were also assessed in these layers as well as in the granule cell layer of the dentate gyrus, stratum oriens of CA3/2, and stratum oriens of CAI. Measurements of neuronal number and region volume were performed for both hemispheres to identify any hemispheric asymmetries. Total neuron numbers and volume in CAI were significantly reduced by 12% (p<0.05) and 17% (p<0.05) respectively due to malnutrition. The volume of the subiculum was significantly reduced in malnourished rats by 12% (p<0.05). Significant asymmetries of total neuron number were found in the CAI and CA3/2 subfields where the right hippocampus had 21% (p=0.001) and 6% (p<0.05) fewer neurons than the left respectively. The CAI subfield of the right hippocampus was also 12% (p<0.01) less in volume than the left. In contrast, the numbers of parvalbumin-immunoreactive interneurons are preserved in the malnourished rats. Thus the ratio of inhibitory cells to excitatory cells is altered in the CAI subfield of the malnourished rats. This alteration is consistent with electrophysiological studies indicating increased inhibition of hippocampal neurons, and may help explain impairments in learning and memory observed in malnourished human populations.