van der Beek Eline M, Wiegant Victor M, Schouten Willem G P, van Eerdenburg Frank J C M, Loijens Leanne W S, van der Plas Carianne, Benning Marjan A, de Vries Hester, de Kloet E Ron, Lucassen Paul J
Human and Animal Physiology Group, Department of Animal Science, Wageningen University, Wageningen, The Netherlands.
Hippocampus. 2004;14(6):688-700. doi: 10.1002/hipo.10213.
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.
尽管应激和高皮质醇血症对啮齿动物海马齿状回（DG）的影响已为人熟知，但对其他物种的了解却很少。对于猪而言，拴系饲养是一种公认的慢性应激源，与限制范式有许多相似之处，行为、自主神经和内分泌功能障碍的显著变化证明了这一点，包括皮质醇节律变平以及高皮质醇血症——所有这些情况都可能威胁大鼠海马的生存能力。在此，我们研究了拴系饲养5个月后猪DG的结构参数与生前测量的基础唾液皮质醇之间的关系。我们进一步研究了左海马半球是否发生了任何神经病理学变化或细胞凋亡改变。体视学分析显示，两个半球中个体动物的DG体积与神经元数量之间存在高度相关性。在个体动物中，左右叶的神经元数量不相关。值得注意的是，基础皮质醇与左DG的体积和神经元数量呈负相关，而与右DG无关。尽管没有明显的神经病理学变化，但DG和齿状回中存在细胞凋亡，而在CA区域则较少。尽管细胞凋亡可检测到的时间窗口较短，但它们在DG中的体视学估计数量与皮质醇呈负相关，而在其他区域则不然。总之，我们的数据首次表明，猪在应激后DG结构、细胞凋亡与基础皮质醇之间的关系存在显著的侧化现象。五个月的慢性应激未能诱发持久的神经病理学变化。尽管细胞凋亡的累积变化可能导致了DG结构的改变，但进一步的研究应揭示应激是否起了作用，或者动物之间的差异是否从出生就存在。然而，目前应激后的侧化现象与应激相关人类疾病中海马体积的侧化变化一致，表明这些影响并不局限于该物种。
