Department of Psychology, University of British Columbia, Vancouver, British Columbia, Canada V6T 1Z4.
J Comp Neurol. 2010 Sep 15;518(18):3662-78. doi: 10.1002/cne.22395.
Chronic elevations in glucocorticoids can decrease the production and survival of new cells in the adult brain. In rat hippocampus, supraphysiological doses of dehydroepiandrosterone (DHEA; a sex steroid precursor synthesized in the gonads, adrenals, and brain) have antiglucocorticoid properties. With male song sparrows (Melospiza melodia), we examined the effects of physiological doses of corticosterone, the primary circulating glucocorticoid in birds, and DHEA on adult neuroplasticity. We treated four groups of nonbreeding sparrows for 28 days with empty (control), corticosterone, DHEA, or corticosterone + DHEA implants. Subjects were injected with BrdU on days 3 and 4. In HVC, a critical song control nucleus, corticosterone and DHEA had independent, additive effects. Corticosterone decreased, whereas DHEA increased, HVC volume, NeuN(+) cell number, and BrdU(+) cell number. Coadministration of DHEA completely reversed the neurodegenerative effects of chronic corticosterone treatment. In an efferent target of HVC, the robust nucleus of the arcopallium (RA), DHEA increased RA volume, but this effect was blocked by coadministration of corticosterone. There were similar antagonistic interactions between corticosterone and DHEA on BrdU(+) cell number in the hippocampus and ventricular zone. This is the first report on the effects of corticosterone treatment on the adult song control circuit, and HVC was the most corticosterone-sensitive song nucleus examined. In HVC, DHEA is neuroprotective and counteracts several pronounced effects of corticosterone. Within brain regions that are particularly vulnerable to corticosterone, such as the songbird HVC and rat hippocampus, DHEA appears to be a potent native antiglucocorticoid.
慢性糖皮质激素升高会减少成年大脑中新细胞的产生和存活。在大鼠海马体中，脱氢表雄酮（DHEA；一种在性腺、肾上腺和大脑中合成的性激素前体）的超生理剂量具有抗糖皮质激素作用。在雄性鸣禽（斑胸草雀，Melospiza melodia）中，我们研究了生理剂量的皮质酮（鸟类中主要的循环糖皮质激素）和 DHEA 对成年神经可塑性的影响。我们用空（对照）、皮质酮、DHEA 或皮质酮+DHEA 植入物处理了四组非繁殖麻雀 28 天。实验对象在第 3 天和第 4 天接受 BrdU 注射。在关键的鸣禽控制核 HVC 中，皮质酮和 DHEA 具有独立的、累加的作用。皮质酮降低，而 DHEA 增加 HVC 体积、NeuN（+）细胞数量和 BrdU（+）细胞数量。DHEA 的共给药完全逆转了慢性皮质酮处理的神经退行性作用。在 HVC 的传出靶区——arcopallium 的粗壮核（RA）中，DHEA 增加了 RA 体积，但这一效应被皮质酮共给药所阻断。皮质酮和 DHEA 对海马体和脑室区 BrdU（+）细胞数量也有类似的拮抗相互作用。这是皮质酮处理对成年鸣禽控制回路影响的首次报告，HVC 是研究的最敏感的鸣禽核。在 HVC 中，DHEA 具有神经保护作用，并抵消了皮质酮的几个显著作用。在特别容易受到皮质酮影响的大脑区域，如鸣禽的 HVC 和大鼠的海马体，DHEA 似乎是一种有效的内源性抗糖皮质激素。
