Allopregnanolone enhances the neurogenesis of midbrain dopaminergic neurons in APPswe/PSEN1 mice
| Autor: | Min Liao, Xie Mq, Yu-Qiang Ding, Shuangshuang Qi, Sixi Chen, Peng Zhou, Zhang P, Chenyou Sun, Gu Qq |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
Male
medicine.medical_specialty Doublecortin Protein Tyrosine 3-Monooxygenase Neurogenesis Subventricular zone Mice Transgenic Plaque Amyloid Substantia nigra Pregnanolone Striatum Amyloid beta-Protein Precursor chemistry.chemical_compound Neural Stem Cells Alzheimer Disease Mesencephalon Lateral Ventricles Internal medicine Presenilin-1 medicine Animals Nootropic Agents Amyloid beta-Peptides biology Pars compacta Dopaminergic Neurons General Neuroscience MPTP Corpus Striatum Doublecortin Disease Models Animal Endocrinology medicine.anatomical_structure nervous system chemistry Mutation biology.protein NeuN Neuroscience |
| Zdroj: | Neuroscience. 290:214-226 |
| ISSN: | 0306-4522 |
| DOI: | 10.1016/j.neuroscience.2015.01.019 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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