Estradiol-induced modulation of estrogen receptor-β and GABA within the adult neocortex:: A potential transsynaptic mechanism for estrogen modulation of BDNF
Estradiol-induced modulation of estrogen receptor-β and GABA within the adult neocortex:: A potential transsynaptic mechanism for estrogen modulation of BDNF
复制标题
DOI：
10.1002/cne.21122
复制
发表时间：
2006-12-01
影响因子：
2.5
通讯作者：
Tuszynsk, Mark H.
中科院分区：
文献类型：
--
作者：
Blurton-Jones, Mathew;Tuszynsk, Mark H.
雌激素影响新皮质中脑源性神经营养因子（BDNF）的表达。然而，产生 BDNF 的皮质神经元不表达可检测水平的核雌激素受体；相反，最丰富的皮质核雌激素受体 ER-β 存在于 GABA 能神经元中，这促使我们检验雌激素影响 BDNF 的假设。通过皮质抑制性中间神经元介导。成年雌性去卵巢大鼠接受急性雌激素替代治疗，并检测皮质GABA、ER-β和ER-β/GABA双标记神经元的数量。注射β-雌二醇后48小时内，ER-β/GABA双标记的鼻周神经元数量减少了28%（与媒介物处理的卵巢切除对照相比，P < 0.01），并且所有表达可检测水平的GABA的细胞减少了19%（P < 0.01）。为了研究雌激素受体、GABA 能神经元和 BDNF 表达细胞之间的潜在关系，对脑切片进行 ER-β、GABA 能和 BDNF 免疫标记物的双重或三重标记。研究结果表明，带有 ER-β 的抑制性神经元投射到其他缺乏核雌激素受体的 GABA 能神经元上；这些抑制性神经元反过来又支配表达 BDNF 的兴奋性细胞。高雌激素状态会降低皮质 GABA 水平，可能会释放对表达 BDNF 的神经元的抑制。这确定了一种假定的两步跨突触机制，其中雌激素的可用性调节抑制性递质的表达，导致 BDNF 表达增加。
Estrogen influences brain-derived neurotrophic factor (BDNF) expression in the neocortex. However, BDNF-producing cortical neurons do not express detectable levels of nuclear estrogen receptors; instead, the most abundant cortical nuclear estrogen receptor, ER-beta, is present in GABAergic neurons, prompting us to test the hypothesis that estrogen effects on BDNF. are mediated via cortical inhibitory interneurons. Adult female ovariectomized rats were provided acute estrogen replacement and the number of cortical GABA, ER-beta, and ER-beta/GABA double-labeled neurons was examined. Within 48 hours of injection of beta-pestradiol, the number of perirhinal neurons double-labeled for ER-beta/GABA was reduced by 28% (P < 0.01 compared to vehicle-treated ovariectomized controls), and all cells expressing detectable levels of GABA were reduced by 19% (P < 0.01). To investigate potential relationships between estrogen receptors, GABAergic neurons, and BDNF-expressing cells, brain sections were double- or triple-labeled for ER-beta, GABAergic, and BDNF immunomarkers. The findings indicated that ER-beta-bearing inhibitory neurons project onto other GABAergic neurons that lack nuclear estrogen receptors; these inhibitory neurons in turn innervate BDNF-expressing excitatory cells. High estrogen states reduce cortical GABA levels, presumably releasing inhibition on BDNF-expressing neurons. This identifies a putative two-step transsynaptic mechanism whereby estrogen availability modulates expression of inhibitory transmitters, resulting in increased BDNF expression.