Pienaar I S, Schallert T, Russell V A, Kellaway L A, Carr J A, Daniels W M U
Division of Medical Physiology, University of Stellenbosch, Western Cape, South Africa.
Restor Neurol Neurosci. 2007;25(5-6):513-26.
The infusion of 6-hydroxydopamine (6-OHDA) into the nigrostriatal pathway in rats is commonly used to produce an animal model of Parkinson's disease (PD). However, most studies use male adult animals only. The present study focused on possible gender differences in vulnerability to 6-OHDA during the early pubertal period when the effects exerted by gonadal steroid hormones are unpronounced.
Young Sprague-Dawley rats, 35 days of age, were given a low vs. a higher dose of 6-OHDA in the medial forebrain bundle (MFB). Control rats received equivalent saline infusions. At 14 days post-surgery the rats were evaluated for forelimb akinesia.
For the higher dose of 6-OHDA the female rats were less impaired than males in making adjustment steps in response to a weight shift and in a vibrissae-evoked forelimb placing test. Tyrosine hydroxylase (TH) immunoreactivity was significantly higher for the female rats.
Early gender differences in cell survival factors and/or other promoters of neuroplasticity may have contributed to the beneficial outcome in the females. For example, NGF was found to be higher in the female rats following administration of DA neurotoxin. It is unclear whether gonadal steroids are involved, and if so, whether female hormones are protective or whether male hormones are prodegenerative. Determining the mechanisms for the improved outcome in the young female rats may lead to potential treatment strategies in PD.
向大鼠黑质纹状体通路注射6-羟基多巴胺（6-OHDA）常用于制备帕金森病（PD）动物模型。然而，大多数研究仅使用成年雄性动物。本研究聚焦于青春期早期，当性腺甾体激素作用不明显时，6-OHDA易感性可能存在的性别差异。
对35日龄的年轻斯普拉格-道利大鼠，在中脑前束（MFB）给予低剂量或高剂量的6-OHDA。对照大鼠接受等量生理盐水注射。术后14天评估大鼠前肢运动不能情况。
对于高剂量的6-OHDA，在应对体重转移的调整步测试和触须诱发前肢放置测试中，雌性大鼠比雄性大鼠受损程度轻。雌性大鼠酪氨酸羟化酶（TH）免疫反应性显著更高。
细胞存活因子和/或其他神经可塑性促进因子的早期性别差异可能导致了雌性大鼠的有益结果。例如，发现给予多巴胺神经毒素后，雌性大鼠体内神经生长因子（NGF）水平更高。尚不清楚性腺甾体激素是否参与其中，如果参与，是雌性激素具有保护作用还是雄性激素具有促退化作用。确定年轻雌性大鼠改善结果的机制可能会带来帕金森病的潜在治疗策略。
