Bastos Cristiane P, Pereira Luciana M, Ferreira-Vieira Talita H, Drumond Luciana E, Massensini André R, Moraes Márcio F D, Pereira Grace S
Núcleo de Neurociências, Departamento de Fisiologia e Biofísica, Instituto de Ciências Biológicas, Brazil.
Centro de Tecnologia e Pesquisa em Magneto-Ressonância, CTPMAG, Universidade Federal de Minas Gerais, Brazil; Universidade Federal de São João Del Rey, Brazil.
Psychoneuroendocrinology. 2015 Jul;57:14-25. doi: 10.1016/j.psyneuen.2015.03.020. Epub 2015 Mar 28.
It is well known that estradiol (E2) replacement therapy is effective on restoring memory deficits and mood disorders that may occur during natural menopause or after surgical ovarian removal (ovariectomy, OVX). However, it is still unknown the effectiveness of acute and localized E2 administration on the effects of chronic OVX. Here we tested the hypothesis that the intra-hippocampal E2 infusion, as well as specific agonists of estrogen receptors (ERs) alpha (ERα) and beta (ERβ), are able to mend novel object recognition (NOR) memory deficit and depressive-like behavior caused by 12 weeks of OVX. We found that both ERα and ERβ activation, at earlier stages of consolidation, recovered the NOR memory deficit caused by 12 w of OVX. Conversely, only the ERβ activation was effective in decreasing the depressive-like behavior caused by 12 w of OVX. Furthermore, we investigated the effect of OVX on hippocampal volume and ERs expression. The structural MRI showed no alteration in the hippocampus volume of 12 w OVX animals. Interestingly, ERα expression in the hippocampus decreased after one week of OVX, but increased in 12 w OVX animals. Overall, we may conclude that the chronic estrogen deprivation, induced by 12 weeks of OVX, modulates the hippocampal ERα expression and induces NOR memory deficit and depressive-like behaviors. Nonetheless, it is noteworthy that the acute effects of E2 on NOR memory and depressive-like behavior are still apparent even after 12 weeks of OVX.
众所周知，雌二醇（E2）替代疗法对于恢复自然绝经期间或手术切除卵巢（卵巢切除术，OVX）后可能出现的记忆缺陷和情绪障碍是有效的。然而，急性和局部给予E2对慢性OVX影响的有效性仍不清楚。在此，我们测试了以下假设：海马内注入E2以及雌激素受体（ER）α（ERα）和β（ERβ）的特异性激动剂能够修复由12周OVX引起的新物体识别（NOR）记忆缺陷和抑郁样行为。我们发现，在巩固的早期阶段，ERα和ERβ的激活均恢复了由12周OVX引起的NOR记忆缺陷。相反，只有ERβ的激活能有效减少由12周OVX引起的抑郁样行为。此外，我们研究了OVX对海马体积和ER表达的影响。结构MRI显示，12周OVX动物的海马体积没有改变。有趣的是，OVX一周后海马中的ERα表达下降，但在12周OVX动物中增加。总体而言，我们可以得出结论，12周OVX诱导的慢性雌激素剥夺调节海马ERα表达，并诱导NOR记忆缺陷和抑郁样行为。尽管如此，值得注意的是，即使在OVX 12周后，E2对NOR记忆和抑郁样行为的急性影响仍然明显。
