Neuronal Number, Volume, and Apoptosis of the Left Dentate Gyrus of Chronically Stressed Pigs Correlate Negatively With Basal Saliva Cortisol Levels

Although the consequences of stress and hypercortisolemia for the rodent hippocampal dentate gyrus (DG) are well known, little is known about other species. For pigs, tethered housing represents a well-established chronic stressor that shares many similarities with restraint paradigms, as evidenced by profound changes in behavior and autonomic and endocrine dysfunction, including flattened cortisol rhythms and hypercortisolemia all conditions that may threaten hippocampal viability in rat. Here, we studied structural parameters of the porcine DG after 5 months of tethered housing in relation to basal saliva cortisol measured antemortem. We further investigated whether any neuropathology or alterations in apoptosis had occurred in the left hippocampal hemisphere. Stereological analysis revealed high correlations between DG volume and neuron number in individual animals in both hemispheres. Within individual animals, neuron numbers of the left and right lobes were not correlated. Notably, basal cortisol was negatively correlated with volume and neuron number of the left, but not the right DG. Although obvious neuropathology was absent, apoptosis was present in DG and alveus and less so in CA areas. Despite the short window of time during which apoptosis is detectable, their stereologically estimated numbers in the DG, but not in other regions, were negatively correlated with cortisol. In conclusion, our data indicate for the first time a profound lateralization in the relationship between DG structure, apoptosis, and basal cortisol after stress in pigs. Five months of chronic stress failed to induce lasting neuropathology. Although accumulating changes in apoptosis could have contributed to the structural DG alterations, further studies should reveal whether stress has been instrumental, or whether the differences between animals were present from birth onward. The present lateralization after stress is, however, consistent with lateralized hippocampal volume changes in stress-related human disorders and suggests that these effects are not limited to this species alone