Ma Yuan-Yi, Kong Shu-Zhen, Yang Li-Jiang, Meng Jin-Lan, Lv Le-Chun, He Min
Department of Physiology, Kunming Medical College, Kunming 650031, China.
Sheng Li Xue Bao. 2007 Dec 25;59(6):753-8.
There are sex differences in some brain areas in mammalians. Parkinson's disease (PD), caused by the mesencephalic substantia nigra (SN) dopaminergic neuronal loss, displays sexual difference, i.e., the incidence is higher and the symptoms are more intense in males than that in females. However, it has not been known whether sexual dimorphisms exist in the SN. Sixty adult Sprague-Dawley rats were randomly divided into 5 groups: (1) Female intact group (F-INT group); (2) Male intact group (M-INT group); (3) Ovariectomized group (OVX group); (4) Castration group (CAST group); (5) Ovariectomized + estrogen-replaced group (OVX-E(2) group): The rats received sequentially physiological dose of estrogen for 3 d from the 7th day after ovariectomization. P50 auditory evoked potential (P50) was recorded for 14 d from electrodes inserted in the rat right SN in quiet and awake state. After recording, the brain tissues were dissected and the tyrosine hydroxylase (TH)-expressing neurons in the compact zone of the SN were counted using immunohistochemical method. The results showed that the number of TH-positive (TH(+)) cells in the SN of normal male animals was less than that in normal female rats (P<0.05), and the T/C ratio of P50 in normal males was significantly less than that in normal females (P<0.01), indicating that there exists sexual difference in function and structure in the SN. No differences in the T/C ratio of P50 or the number of TH(+) cells were found between M-INT and CAST groups. The T/C ratio of P50 and the number of TH(+) cells in the SN in OVX group were reduced significantly compared with those in F-INT group (P<0.01). There was no significant difference in the T/C ratio of P50 and the number of TH(+) cells in the SN between OVX- E(2) and F-INT groups 15-20 d after estrogen replacement, suggesting that estrogen can promote the survival and functional recovery of dopaminergic neurons in the SN. The results suggest that there exist sex-specific differences in the dopaminergic neurons in the SN structurally and functionally. The difference of estrogen level in cerebra between male and female animals may account for the sexual differences. Endogenous estrogen plays an important role in maintaining the integrity and modulating the functional activity of dopamine system in the SN.
哺乳动物的某些脑区存在性别差异。由中脑黑质(SN)多巴胺能神经元缺失引起的帕金森病(PD)存在性别差异,即男性的发病率更高,症状比女性更严重。然而,SN中是否存在性别二态性尚不清楚。将60只成年Sprague-Dawley大鼠随机分为5组:(1)雌性完整组(F-INT组);(2)雄性完整组(M-INT组);(3)去卵巢组(OVX组);(4)阉割组(CAST组);(5)去卵巢+雌激素替代组(OVX-E(2)组):大鼠在去卵巢后第7天开始连续3天接受生理剂量的雌激素。在安静清醒状态下,从插入大鼠右侧SN的电极记录14天的P50听觉诱发电位(P50)。记录后,解剖脑组织,采用免疫组织化学方法计数SN致密部中表达酪氨酸羟化酶(TH)的神经元。结果显示,正常雄性动物SN中TH阳性(TH(+))细胞的数量少于正常雌性大鼠(P<0.05),正常雄性动物P50的T/C比值显著低于正常雌性动物(P<0.01),表明SN在功能和结构上存在性别差异。M-INT组和CAST组之间在P50的T/C比值或TH(+)细胞数量上没有差异。与F-INT组相比,OVX组SN中P50的T/C比值和TH(+)细胞数量显著降低(P<0.01)。雌激素替代15 - 20天后,OVX-E(2)组和F-INT组SN中P50的T/C比值和TH(+)细胞数量没有显著差异,表明雌激素可以促进SN中多巴胺能神经元的存活和功能恢复。结果表明,SN中的多巴胺能神经元在结构和功能上存在性别特异性差异。雄性和雌性动物大脑中雌激素水平的差异可能是造成性别差异的原因。内源性雌激素在维持SN中多巴胺系统的完整性和调节其功能活动方面起着重要作用。