Leussis Melanie P, Andersen Susan L
Laboratory of Developmental Neuropharmacology, Department of Psychiatry, Harvard Medical School and McLean Hospital, Belmont, Massachusetts 02478, USA.
Synapse. 2008 Jan;62(1):22-30. doi: 10.1002/syn.20462.
Sex differences in depressive symptoms emerge during adolescence, with females more at risk than males. However, adverse life events during development have greater impact on males. An animal model that incorporates behavioral and anatomical changes following adolescent stress is needed.
Sprague-Dawley rats were exposed to social stress (SS; isolation housing during P30-35) or remained group-housed (GRP) and tested in the forced swim test (FST), the triadic learned helplessness model (LH), and the elevated plus maze. Western immunoblots of myelin basic protein (MBP) and synaptophysin (SVP) and spinophillin indexed synaptic and dendritic plasticity, respectively.
At P36, SS increased climbing behavior in both sexes, and decreased the latency to immobility in females following a 15 min inescapable swim in the FST. Depressive-like behaviors were differentially elevated in both sexes 24 h later. GRP females exhibited higher levels of depression-related behaviors than GRP males in both FST and LH paradigms. SS significantly increased depressive behaviors in the FST in males, and impaired their ability to escape shock previously conditioned to be controllable. SS decreased open arm time in females only. The greatest reductions in synaptic plasticity proteins were observed in the prefrontal cortex: spinophillin (19.1%), SVP (7.9%), and MBP (48.7%, males only). Smaller reductions in spinophillin were observed in the hippocampus and amygdala.
Adolescent separation produces both behavioral and neural changes associated with stress-related depression and anxiety. Additional work is needed to improve our understanding of stress as it relates to depression during this vulnerable period of development.
抑郁症状的性别差异在青春期出现，女性比男性面临更高风险。然而，发育过程中的不良生活事件对男性影响更大。需要一种纳入青春期应激后行为和解剖学变化的动物模型。
将斯普拉格-道利大鼠暴露于社会应激（SS；在P30 - 35期间单独饲养）或继续群居（GRP），并在强迫游泳试验（FST）、三元习得性无助模型（LH）和高架十字迷宫中进行测试。髓鞘碱性蛋白（MBP）和突触素（SVP）的蛋白质免疫印迹以及棘状蛋白分别反映突触和树突可塑性。
在P36时，SS增加了两性的攀爬行为，并缩短了雌性大鼠在FST中进行15分钟不可逃避游泳后静止不动的潜伏期。24小时后，两性的抑郁样行为均有不同程度升高。在FST和LH范式中，GRP雌性比GRP雄性表现出更高水平的抑郁相关行为。SS显著增加了雄性大鼠在FST中的抑郁行为，并损害了它们逃避先前条件性可控制电击的能力。SS仅降低了雌性大鼠的开放臂停留时间。在额叶皮质观察到突触可塑性蛋白的最大减少：棘状蛋白（19.1%）、SVP（7.9%）和MBP（仅雄性为48.7%）。在海马体和杏仁核中观察到棘状蛋白的减少幅度较小。
青春期分离会产生与应激相关的抑郁和焦虑相关的行为和神经变化。需要进一步开展工作，以增进我们对这一发育脆弱期与抑郁相关应激的理解。
