Lee Diane W, Fernando Gowry, Peterson R Scott, Allen Timothy A, Schlinger Barney A
Department of Psychology, California State University, Long Beach, California 90840, USA.
Dev Neurobiol. 2007 Jul;67(8):1107-17. doi: 10.1002/dneu.20399.
Estrogens influence neuronal differentiation, migration, and survival in intact brains. In injured brains, estrogens can also be neuroprotective. In Experiment 1, following a unilateral penetrating injury to the hippocampus (HP), adult female zebra finches were injected once with BrdU to label mitotic cells then sacrificed 2 h, 1 day, or 7 days postinjection. Cell proliferation was dramatically enhanced in the ipsilateral HP, as well as in neuroproliferative areas including the subventricular zone (SVZ) proximal to the injury. This increase was seen at all time points investigated. Ovariectomy (OVX) substantially suppressed proliferation bilaterally especially in the SVZ indicating that gonadal hormones influenced cell proliferation in both the intact and injured hemisphere. To determine if estrogens were directly involved, estrogen was depleted in Experiment 2 through either OVX or administration of the aromatase inhibitor fadrozole (FAD). Birds were implanted with estradiol or blank followed 2 weeks later by a unilateral penetrating lesion to the HP. Injury-induced substantial proliferation, which was again significantly suppressed bilaterally in both OVX and FAD birds. Estrogen replacement reversed this effect in FAD but not OVX birds therefore the suppression following OVX may be due in part to nonestrogenic influences. Suppression of cell birth in FAD birds was indeed due to the removal of endogenous sources of estrogen. Results therefore indicate that estrogens are directly involved in the brain's response to injury and may be acting to provide a rich environment for the production and perhaps protection of new cells.
雌激素影响完整大脑中神经元的分化、迁移和存活。在受损大脑中，雌激素也具有神经保护作用。在实验1中，成年雌性斑胸草雀单侧海马体（HP）遭受穿透性损伤后，一次性注射溴脱氧尿苷（BrdU）以标记有丝分裂细胞，然后在注射后2小时、1天或7天处死。同侧海马体以及包括损伤近端室下区（SVZ）在内的神经增殖区域的细胞增殖显著增强。在所有研究的时间点均观察到这种增加。卵巢切除术（OVX）双侧显著抑制增殖，尤其是在室下区，表明性腺激素影响完整半球和受损半球的细胞增殖。为了确定雌激素是否直接起作用，在实验2中通过卵巢切除术或给予芳香化酶抑制剂法倔唑（FAD）使雌激素耗竭。给鸟类植入雌二醇或空白对照，2周后单侧穿透损伤海马体。损伤诱导大量增殖，在卵巢切除和法倔唑处理的鸟类中双侧再次显著受到抑制。雌激素替代在法倔唑处理的鸟类中逆转了这种效应，但在卵巢切除的鸟类中没有，因此卵巢切除后的抑制可能部分归因于非雌激素的影响。法倔唑处理的鸟类中细胞生成的抑制确实是由于内源性雌激素来源的去除。因此，结果表明雌激素直接参与大脑对损伤的反应，可能是在为新细胞的产生以及可能的保护提供丰富环境。
