Effect of allopregnanolone on the dopaminergic neurons in the substantia nigra of Alzheimer’s disease mice 

doi:10.3969/j.issn.0529-1356.2013.02.006

Abstract

Abstract:

Objective The present study was undertaken to evaluate the effects of allopregnanolone (APα) on neurogenesis of dopaminergic neurons by analyzing the numbers of dopaminergic neurons and newly formed dopaminergic neurons in the substantia nigra pars compacta (SNpc) of Alzheimer’s disease (AD) mice. Methods Experiments were performed using 3-month-old male double transgenic amyloid precursor protein with presenilin (APP/PS1) mouse model of AD (2xTg-AD) and non-transgenic (non-Tg) background mice. These mice were administered with APα or phosphate buffer saline (PBS), respectively. Following 24 days, six mice in each group were performed behavior testing by open-field test. The brain tissue from another 6 mice in each group was taken out and post-fixed and the numbers of tyrosine hydroxylase (TH) expressing dopaminergic neurons and TH expression were observed and analyzed in the SNpc region by the immunohistochemistry, unbiased stereology and optical intensity. In addition, the numbers of TH/bromodeoxyuridine (BrdU) double labeled dopaminergic neurons were counted by the immunofluorescent method. Results As compared with the Non-Tg+PBS mice, the data for 2xTg-AD+PBS mice were obviously decreased in the ambulation of open-field test (P ＜0.01), the intensities of TH immunohistochemical activity (P ＜0.05), the numbers of dopaminergic neurons and BrdU/TH double labeled neurons in the SNpc regions (P ＜0.05). As compared with the 2xTg-AD+PBS mice, the data for 2xTg-AD+APα mice was obviously increased in the ambulation of openfield test (P ＜0.05), the numbers of dopaminergic neurons ( P ＜0.05) and BrdU/TH double labeled neurons in the SNpc regions ( P ＜0.01). However, the intensities of TH immunohistochemical activity didn’t alter significantly between the 2xTg-AD+PBS and 2xTg-AD+APα mice (P＞0.05). Conclusion These results indicate that APα may ameliorate the loss of numbers of dopaminergic neurons by increasing the numbers of newly formed dopaminergic neurons in the SNpc of 2xTg-AD mice. These results suggest the APα may have a potential therapeutic efficacy in neurogenesis.

Key words:

Allopregnanolone, Dopaminergic neurons, Neurogenesis;Alzheimer’s disease , Immunohistochemistry , Immunofluorescent staining , APP/PS1 double transgenic AD mouse

WANG Qiong-sa, QI Shuang-shuang, ZHOU Peng, ZHANG Chi-hao, CUI Huai-rui, CHEN Shi-xin, SUN Chen-you* . Effect of allopregnanolone on the dopaminergic neurons in the substantia nigra of Alzheimer’s disease mice [J]. AAS, 2013, 44(2 ): 176-181.

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