Neuroendocrine adaptation to stress in pigs, CRH and vasopressin in the paraventricular nucleus

Differences in coping strategy present at birth as well as housing conditions may influence autonomic and endocrine stress responses.In rodents,corticotropin-releasing hormone (CRH) and vasopressin (VP) signaling in theparaventricularnucleus (PVN) plays an important role in stress responses.Stress is known to induce expression of VP in PVN-CRH neurons, with the degree of VP expression relating to duration and intensity of the stress.Moreover, there is evidence that the activity of these systems is altered in stress-induced sensitization. This suggests that the functional state of CRH and VP systems, likely also in the pig PVN, could be used as a neurobiological index of stress vulnerability.

The aim of the thesis was to asses in pigs the effects ofindividual coping strategy (high and low resisting, HR and LR respectively), and rearing and housing conditions on the susceptibility of pigs to stress sensitization.Changes in CRH and VP expression in the PVN were studied in female and also male pigs with different coping strategies subjected to different housing conditions using immunocytochemistry and in situ hybridization techniques.

We found a clear sex difference in both CRH and VP peptide content in the PVN, i.e. male pigs showed higher VP and CRH peptide content compared to female pigs. This confirms and extends previous reports of the existence of a sexually dimorphic regulation of the HPA axis.The results of this studysuggests that the housing conditions tested, although they clearly affected some behavioral and endocrine parameters, were not contrasting enough with respects to stress load to result in changes in the activity of the HPA axis at the hypothalamic level. Individual housing (IND), however, did affect the HPA axis, with a clear, coping strategy dependent difference on VP peptide and CRH mRNA, but not on CRH peptide levels. The PVN inIND HR pigs contained higher VP peptide levels compared to group housed (GRO) HR and IND LR gilts. Moreover, we found that the absolute number, but not the percentage of cells showing co-localization of VP and CRH peptide was increased in IND HR gilts compared to GRO HR gilts.We suggest that the higherlevels of VP peptide in the medial region of the PVN in IND HR pigs playsa role inpotentiatingthe actions of CRH to stimulate ACTH secretion from the anterior pituitary.Furthermore, IND LR gilts showed increased levels of CRH mRNA compared to GRO LR and IND HR gilts, which suggests that LR pigs react to chronic housing stress with an up-regulation of CRH transcription.

The experiments described in this thesis provide evidence that pigs characterized with different coping strategies at early age, differ as adults in the way they adapt to individual housing at the level of the PVN. The differences found in CRH and VP levels in the PVN support the differences in basal behavioral and physiological variables between these animals that became evident under chronic stress. Moreover, the changes in activity of CRH and VP observed are reminiscent to those observed in human psychopathology (e.g. depression), suggesting that these changes may be interpreted as (pre) pathological signs in the pig. This suggests that individual housing is not an optimal housing condition for both HR and LR pigs. Based on these results, we conclude that housing condition likely increases the susceptibility to stress in both HR and LR gilts. Selection of pigs for coping strategy to maintain common practice of individual housing of breeding pigs will therefore not benefit the welfare of the animals. To improve pig welfare and minimize the risk of stress-related diseases, the focus should be on optimizing the pigs' housing conditions.