| First Author | Zhang P | Year | 2015 |
| Journal | Neuroscience | Volume | 290 |
| Pages | 214-26 | PubMed ID | 25637494 |
| Mgi Jnum | J:224573 | Mgi Id | MGI:5688267 |
| Doi | 10.1016/j.neuroscience.2015.01.019 | Citation | Zhang P, et al. (2015) Allopregnanolone enhances the neurogenesis of midbrain dopaminergic neurons in APPswe/PSEN1 mice. Neuroscience 290:214-26 |
| abstractText | An earlier study has demonstrated that exogenous allopregnanolone (APalpha) 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 APalpha treatment. We performed a deeper research in another AD mouse model, 4-month-old male APPswe/PSEN1 double transgenic AD mouse (2xTgAD) by measuring APalpha concentration and counting immunopositive neurons using enzyme-linked immunosorbent assay (ELISA) and unbiased stereology. It was found that endogenous APalpha level and the number of TH-positive neurons were reduced in the 2xTgAD mice, and these reductions were present prior to the appearance of beta-amyloid (Abeta)-positive plaques. Furthermore, a single 20mg/kg of exogenous APalpha 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 APalpha 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 APalpha is implicated in the loss of midbrain dopaminergic neurons in the 2xTgAD mice, and exogenous APalpha-induced a significant increase in the new-born dopaminergic neurons might be derived from the proliferating and differentiation of neural stem niche of SVZ. |
