ALLOPREGNANOLONE ENHANCES THE NEUROGENESIS OF MIDBRAIN DOPAMINERGIC NEURONS IN APPSWE/PSEN1 MICE

作者：Zhang P; Xie M Q; Ding Y Q; Liao M; Qi S S; Chen S X; Gu Q Q; Zhou P; Sun C Y^*

来源：Neuroscience, 2015, 290: 214-226.

DOI：10.1016/j.neuroscience.2015.01.019

• Alzheimer's disease
• substantia nigra pars compacta
• dopaminergic neuron
• allopregnanolone
• APPswe/PSEN1 mouse
• neurogenesis

An earlier study has demonstrated that exogenous allopregnanolone (AP alpha) 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 AP alpha treatment. We performed a deeper research in another AD mouse model, 4-month-old male APPswe/PSEN1 double transgenic AD mouse (2xTgAD) by measuring AP alpha concentration and counting immunopositive neurons using enzyme-linked immunosorbent assay (ELISA) and unbiased stereology. It was found that endogenous APa 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 (Ab)-positive plaques. Furthermore, a single 20 mg/kg of exogenous AP alpha 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 AP alpha 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 AP alpha is implicated in the loss of midbrain dopaminergic neurons in the 2xTgAD mice, and exogenous AP alpha-induced a significant increase in the new-born dopaminergic neurons might be derived from the proliferating and differentiation of neural stem niche of SVZ.

• 出版日期2015-4-2
• 单位温州医科大学