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Effect of allopregnanolone on the dopaminergic neurons in the substantia nigra of APPswe / PSEN1 mice
Author(s): ZHANG Peng, QI Shuang-shuang, XIE Ming-qi, LIAO Min, LIU Fen, ZHOU Peng, CUI Huai-rui, SUN Chen-you, Department of Anatomy, School of Basic Medical Sciences of Wenzhou Medical University, Institute of Neuroscience, School of Basic Medical Sciences of Wenzhou Medical University, Department of Pharmacy, the 2nd Affiliated Hospital & Yuying Children’s Hospital of Wenzhou Medical University, Department of Histology and Embryology, School of Basic Medical Sciences of Wenzhou Medical University
Pages: 317-
323
Year: 2015
Issue:
3
Journal: Acta Anatomica Sinica
Keyword: Alzheimer’s disease; Substantia nigra; Allopregnanolone; Neurogenesis; Immunofluorescence; Double-transgenic AD mouse;
Abstract: Objective To evaluate the effect of allopregnanolone( APα) on the tyrosine hydroxylase( TH)-positive neuron in the substantia nigra( SN) of the transgenic mouse of Alzheimer ’s disease( AD). Methods Immunopositive cells were observed and measured in the 4-month-old male mice( n = 31) using an immuno-staining technique. Results The APα level and the number of TH-positive neurons were reduced in the double-transgenic AD mouse( 2 × Tg AD),and these reductions were present prior to the appearance of β-amyloid positive plaques. APαtreatment prevented the decrease of the total number of neurons,TH-positive neurons and TH / bromodeoxyuridine( Brd U)-double positive neurons in the SN of 2 × Tg AD mice although the decreased intensities of TH-positive neural fibers were not rescued in the striatum. In addition,APα administration had an apparent increase in the number of new-born mature neurons without affecting the new-generating astrocytes in the SN of 2 × Tg AD mice. Conclusion A lower level of endogenous APα is implicated in the loss of dopaminergic neurons in the 2 × Tg AD mice. Exogenous APα can recover the reducing TH-positive neurons by promoting their neurogenesis in the 2 × Tg AD mice.
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