title: Allopregnanolone enhances the neurogenesis of midbrain dopaminergic neurons in APPswe/PSEN1 mice.
abstract: An earlier study has demonstrated that exogenous allopregnanolone (APα) can reverse the reduction of tyrosine hydroxylase (TH)-positive neurons in the substantia nigra pars compacta (SNpc) of 3-month-old male triple transgenic Alzheimer's disease mouse (3xTgAD). This paper is focused on further clarifying the origin of these new-born TH-positive neurons induced by exogenous APα treatment. We performed a deeper research in another AD mouse model, 4-month-old male APPswe/PSEN1 double transgenic AD mouse (2xTgAD) by measuring APα concentration and counting immunopositive neurons using enzyme-linked immunosorbent assay (ELISA) and unbiased stereology. It was found that endogenous APα level and the number of TH-positive neurons were reduced in the 2xTgAD mice, and these reductions were present prior to the appearance of β-amyloid (Aβ)-positive plaques. Furthermore, a single 20mg/kg of exogenous APα treatment prevented the decline of total neurons, TH-positive neurons and TH/bromodeoxyuridine (BrdU) double-positive neurons in the SNpc of 2xTgAD mice although the decreased intensity of TH-positive fibers was not rescued in the striatum. It was also noted that exogenous APα administration had an apparent increase in the doublecortin (DCX)-positive neurons and DCX/BrdU double-positive neurons of subventricular zone (SVZ), as well as in the percentage of neuronal nuclear antigen (NeuN)/BrdU double-positive neurons of the SNpc in the 2xTgAD mice. These findings indicate that a lower level of endogenous APα is implicated in the loss of midbrain dopaminergic neurons in the 2xTgAD mice, and exogenous APα-induced a significant increase in the new-born dopaminergic neurons might be derived from the proliferating and differentiation of neural stem niche of SVZ.
authors: Department of Anatomy, School of Basic Medical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang Province 325035, China; Institute of Neuroscience, School of Basic Medical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang Province 325035, China.
authors: P
authors: P
authors: Zhang
authors: Department of Anatomy, School of Basic Medical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang Province 325035, China; Institute of Neuroscience, School of Basic Medical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang Province 325035, China.
authors: M Q
authors: MQ
authors: Xie
authors: Institute of Neuroscience, School of Basic Medical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang Province 325035, China.
authors: Y-Q
authors: YQ
authors: Ding
authors: Institute of Neuroscience, School of Basic Medical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang Province 325035, China; Department of Histology and Embryology, School of Basic Medical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang Province 325035, China.
authors: M
authors: M
authors: Liao
authors: Department of Pharmacy, Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province 325000, China.
authors: S S
authors: SS
authors: Qi
authors: Department of Anatomy, School of Basic Medical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang Province 325035, China.
authors: S X
authors: SX
authors: Chen
authors: Department of Anatomy, School of Basic Medical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang Province 325035, China; Institute of Neuroscience, School of Basic Medical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang Province 325035, China.
authors: Q Q
authors: QQ
authors: Gu
authors: Department of Anatomy, School of Basic Medical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang Province 325035, China.
authors: P
authors: P
authors: Zhou
authors: Department of Anatomy, School of Basic Medical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang Province 325035, China; Institute of Neuroscience, School of Basic Medical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang Province 325035, China. Electronic address: sunchenyou1972@aliyun.com.
authors: C Y
authors: CY
authors: Sun
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism; D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D004195:Disease Models, Animal; D059290:Dopaminergic Neurons / Q000187:drug effects* / Q000473:pathology / Q000502:physiology; D000089662:Doublecortin Protein; D020547:Lateral Ventricles / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D008297:Male; D008636:Mesencephalon / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D008822:Mice, Transgenic; D009154:Mutation; D058953:Neural Stem Cells / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D055495:Neurogenesis / Q000187:drug effects* / Q000502:physiology; D018697:Nootropic Agents / Q000494:pharmacology*; D058225:Plaque, Amyloid / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D011280:Pregnanolone / Q000494:pharmacology*; D053764:Presenilin-1 / Q000235:genetics / Q000378:metabolism; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: C545487:APP protein, human; D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; C000714847:Dcx protein, mouse; D000089662:Doublecortin Protein; D018697:Nootropic Agents; C508853:PSEN1 protein, human; D053764:Presenilin-1; D011280:Pregnanolone; D014446:Tyrosine 3-Monooxygenase
keywords: APPswe/PSEN1 mouse; Alzheimer’s disease; allopregnanolone; dopaminergic neuron; neurogenesis; substantia nigra pars compacta