Institute of Basic Medical Sciences, National Cheng Kung University College of Medicine, Tainan 70101, Taiwan, ROC.
Psychoneuroendocrinology. 2013 Mar;38(3):425-37. doi: 10.1016/j.psyneuen.2012.07.002. Epub 2012 Jul 23.
The presence of companions can reverse the stressor-induced decrease in neurogenesis in mouse dentate gyrus (DG). In this study, we decided to study the underlying mechanisms of the companions' protective effect and to assess whether two DG neurogenesis-related memories, cocaine-induced conditioned place preference (CPP) and spatial memory, can be affected by our stressor and companions. Neurotrophin levels in DG were measured, in this regard, to reveal their roles in mediating the stressors' and companions' effect. We found that the stressor did not affect NT-3 but acutely decreased NGF and BDNF levels in DG. The presence of companions abolished these stressor-decreased NGF and BDNF levels. Neither the stressor nor the presence of companions affected TrkA, TrkB or TrkC expression in DG. Pre-exposure to the stressor rendered deficits in cocaine-induced CPP and spatial memory, while companions reversed the stressor-decreased cocaine-induced CPP. Intra-ventricular infusion with K252a, a mixed TrkA and TrkB antagonist, did not affect the protective effects of companions on local NGF, BDNF levels in DG, but abolished the companions' protective effects against the stressor-decreased DG neurogenesis and cocaine-induced CPP. Systemic pretreatment with 7,8-dihydroxyflavone (DHF), a selective TrkB agonist, did not affect baseline, the stressor-stimulated corticosterone (CORT) secretion or local NGF, BDNF levels in DG, but in part mimicked companions' protective effects. These results, taken together, indicate that stressor-decreased NGF and BDNF levels in DG could be involved in the stressor-decreased DG neurogenesis and cocaine conditioning. The presence of companions reverses the stressor-decreased DG neurogenesis and cocaine conditioning possibly by restoring BDNF and NGF levels in DG.
同伴的存在可以逆转应激引起的小鼠齿状回（DG）神经发生减少。在这项研究中，我们决定研究同伴保护作用的潜在机制，并评估应激和同伴是否会影响两种与 DG 神经发生相关的记忆，即可卡因诱导的条件性位置偏好（CPP）和空间记忆。为此，测量了 DG 中的神经营养因子水平，以揭示它们在介导应激和同伴作用中的作用。我们发现，应激源不会影响 NT-3，但会急性降低 DG 中的 NGF 和 BDNF 水平。同伴的存在消除了这些应激源降低的 NGF 和 BDNF 水平。应激源或同伴的存在都不会影响 DG 中的 TrkA、TrkB 或 TrkC 表达。预先暴露于应激源会导致可卡因诱导的 CPP 和空间记忆缺陷，而同伴则逆转了应激源降低的可卡因诱导的 CPP。脑室内输注混合 TrkA 和 TrkB 拮抗剂 K252a 不会影响同伴对 DG 局部 NGF 和 BDNF 水平的保护作用，但消除了同伴对 DG 神经发生减少和可卡因诱导的 CPP 的保护作用。系统给予选择性 TrkB 激动剂 7,8-二羟基黄酮（DHF）预处理不会影响基线、应激刺激的皮质酮（CORT）分泌或 DG 中的局部 NGF 和 BDNF 水平，但部分模拟了同伴的保护作用。这些结果表明，DG 中应激源降低的 NGF 和 BDNF 水平可能参与了应激源降低的 DG 神经发生和可卡因条件作用。同伴的存在通过恢复 DG 中的 BDNF 和 NGF 水平逆转了应激源降低的 DG 神经发生和可卡因条件作用。
