Laboratory of Molecular Signalling, Cognitive and Systems Neuroscience Group, The Babraham Institute, Babraham, Cambridge CB22 3AQ, UK.
Horm Behav. 2011 Jan;59(1):114-22. doi: 10.1016/j.yhbeh.2010.10.016. Epub 2010 Nov 4.
Establishing clear effects of gender and natural hormonal changes during female ovarian cycles on cognitive function has often proved difficult. Here we have investigated such effects on the formation and long-term (24 h) maintenance of social recognition memory in mice together with the respective involvement of α- and β-estrogen receptors using α- and β-estrogen receptor knockout mice and wildtype controls. Results in wildtype animals showed that while females successfully formed a memory in the context of a habituation/dishabituation paradigm at all stages of their ovarian cycle, only when learning occurred during proestrus (when estrogen levels are highest) was it retained after 24 h. In α-receptor knockout mice (which showed no ovarian cycles) both formation and maintenance of this social recognition memory were impaired, whereas β-receptor knockouts showed no significant deficits and exhibited the same proestrus-dependent retention of memory at 24 h. To investigate possible sex differences, male α- and β-estrogen receptor knockout mice were also tested and showed similar effects to females excepting that α-receptor knockouts had normal memory formation and only exhibited a 24 h retention deficit. This indicates a greater dependence in females on α-receptor expression for memory formation in this task. Since non-specific motivational and attentional aspects of the task were unaffected, our findings suggest a general α-receptor dependent facilitation of memory formation by estrogen as well as an enhanced long-term retention during proestrus. Results are discussed in terms of the differential roles of the two estrogen receptors, the neural substrates involved and putative interactions with oxytocin.
确定女性卵巢周期中性别和天然激素变化对认知功能的明确影响通常很困难。在这里，我们使用α-和β-雌激素受体敲除小鼠和野生型对照，研究了这些对小鼠社会识别记忆的形成和长期（24 小时）维持的影响，以及各自涉及的α-和β-雌激素受体。野生型动物的结果表明，虽然女性在整个卵巢周期的各个阶段都能在习惯/习惯破坏范式中成功形成记忆，但只有在发情前期（雌激素水平最高时）学习时，记忆才能在 24 小时后保留。在α-受体敲除小鼠（没有卵巢周期）中，这种社会识别记忆的形成和维持都受到损害，而β-受体敲除小鼠则没有明显的缺陷，并且在 24 小时后表现出相同的发情前期依赖的记忆保留。为了研究可能存在的性别差异，还测试了雄性α-和β-雌激素受体敲除小鼠，结果与雌性相似，除了α-受体敲除小鼠具有正常的记忆形成，仅表现出 24 小时保留缺陷。这表明在这项任务中，女性对记忆形成的α-受体表达的依赖性更大。由于任务的非特异性动机和注意力方面不受影响，我们的发现表明雌激素对记忆形成的一般α-受体依赖性促进作用，以及发情前期的长期保留增强。结果从两个雌激素受体的不同作用、涉及的神经基质以及与催产素的潜在相互作用方面进行了讨论。
