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大鼠黑质多巴胺能神经元的二型性

马元怡, 孔淑珍, 杨黎江, 孟金兰, 吕乐春, 何敏

昆明医学院生理学教研室.云南,昆明 650031

摘要

成年哺乳动物的某些脑区存在性别差异，即二型性，但中脑黑质是否存在性分化目前不清楚。该文探讨成年大鼠中脑黑质是否存在二性型。60只成年大鼠分成5组：(1)正常雌鼠对照组；(2)正常雄鼠对照组；(3)去卵巢组；(4)去睾丸组；(5)去卵巢后回补雌激素组，该组大鼠在去卵巢后的d7开始连续3 d给予生理剂量的雌激素回补。所有大鼠在右侧黑质埋置记录电极，在清醒和安静的生理状态下连续14 d记录黑质的P50听觉诱发电位(P50)，之后作黑质酪氨酸羟化酶(tyrosine hydroxylase, TH)免疫组织化学染色，检查TH阳性(TH~(+))细胞数量和形态变化。结果表明，正常成年雄鼠黑质的TH~(+)细胞数量较雌鼠少22.47% ({sl P}<0.05)，P50的T/C值也降低34.72% ({sl P}<0.01)，提示正常成年大鼠黑质在结构和功能上存在二型性。去睾丸大鼠黑质的TH~(+)细胞数量、形态和P50的T/C值与正常雄鼠相比，无显著性变化({sl P}>0.05)，而去卵巢大鼠黑质的TH~(+)细胞量和P50的T/C值与正常雌鼠相比，其黑质TH~(+)细胞数量减少28.09% ({sl P}<0.01)，P50的T/C值降低30.85%({sl P}<0.01)。对去卵巢大鼠短时间内补给3 d生理剂量的雌激素，15---20 d后可观察到其黑质TH+细胞数量、形态和P50的T/C值基本恢复到去卵巢前水平({sl P}>0.05)。结果提示，大鼠中脑黑质的多巴胺能神经元在数量、结构和功能活动上存在性别差异；内源性雌激素在维持黑质多巴胺系统完整性及调节其功能活动中起重要作用。

关键词： 脑的二型性; 雌激素; 黑质; 多巴胺神经元; 感觉门控; P50听觉诱发电位; 酪氨酸羟化酶

Sexual dimorphisms of dopaminergic neurons in rat substantia nigra

Ma Yuanyi, Kong Shuzhen, Yang Lijiang, Meng Jinlan, Lu Lechun, He Min

Department of Physiology, Kunming Medical College.Kunming 650031,Yunnan

Abstract

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, which reflects the male preponderance. To explore the mechanism of the difference, 60 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) ovariectomy + estrogen-replaced group (OVX-E_(2) group). The rats received sequentially physiological dose of estrogen for 3 d after ovariectomization for 7 d. P50 auditory evoked potentials were recorded for 14 d from electrodes inserted in the right SN of the rats 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 female rats (P<0.05), and the T/C ratio of P50 in males was significantly less than that in females (P<0.01), indicating that there exists sexual difference in function and structure in the SN. No differences in T/C ratio of P50 or the number of TH+ cells were found between M-INT and CAST groups. 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 T/C ratio of P50 and the number of TH+ cells in the SN between OVX-E_(2) and F-INT groups (P>0.05) 15-20 d after estrogen replacement. These results indicate that estrogen can promote survival of the dopamine neurons and recovery of function of these neurons in the SN. Conclusion: The results in the present study suggest that there exist sex-specific differences in the dopaminergic neurons in the SN structurally and functionally. Different levels of estrogen in cerebra between male and female animals may account for the sex differences. Endogenous estrogen plays an important role in maintaining the integrity and modulating the functional activity of dopamine system in the SN.

Key words: sex dimorphisms in brain;Estrogen;Substantia nigra;dopaminergic neuron;sensory gating;P50 auditory evoked potential;tyrosine hydroxylase

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引用本文：

马元怡, 孔淑珍, 杨黎江, 孟金兰, 吕乐春, 何敏. 大鼠黑质多巴胺能神经元的二型性[J]. 生理学报 2007; 59 (6): 753-758.

Ma Yuanyi, Kong Shuzhen, Yang Lijiang, Meng Jinlan, Lu Lechun, He Min. Sexual dimorphisms of dopaminergic neurons in rat substantia nigra. Acta Physiol Sin 2007; 59 (6): 753-758 (in Chinese with English abstract).