Allopregnanolone Increases the Number of Dopaminergic Neurons in Substantia Nigra of a Triple Transgenic Mouse Model of Alzheimer%26apos;s Disease

作者：Sun Chenyou; Ou Xiaoming; Farley Jerry M; Stockmeier Craig; Bigler Steven; Brinton Roberta Diaz; Wang Jun Ming^*

来源：Current Alzheimer Research, 2012, 9(4): 473-480.

DOI：10.2174/156720512800492567

• Allopregnanolone
• neurogenesis
• tyrosine hydroxylase (TH)
• substantia nigra
• dopaminergic neurons

More than a third of Alzheimer%26apos;s disease (AD) patients show nigrostriatal pathway disturbances, resulting in akinesia (inability to initiate movement) and bradykinesia (slowness of movement). The high prevalence of this dysfunction of dopaminergic neuron in the nigrostriatal pathway in AD suggests that the risk factors for AD appear also significant risk factors for substantia nigra pars compacta (SNpc) lesions. Previously, we have demonstrated that allopregnanolone (AP alpha) promotes neurogenesis and improves the cognitive function in a triple transgenic mouse model of AD (3xTgAD). In this study, we sought to exam 1) the SNpc lesions in 3xTgAD mice and 2) the impact of AP alpha on promoting the regeneration of new dopaminergic neurons in SNpc of the 3xTgAD mice. The number of Nissl-stained total neurons, tyrosine hydroxylase (TH) positive neurons, and BrdU/TH double positive newly formed neurons were analyzed with unbiased stereology. In the SNpc of 3xTgAD mice, TH positive neurons was 47 +/- 18 % (p = 0.007), total neurons was 62 +/- 11.6 % (p = 0.016), of those in the SNpc of non-Tg mice, respectively. APa treatment increased the TH positive neurons in the SNpc of 3xTgAD mice to 93.2 +/- 18.5 % (p = 0.021 vs. 3xTgAD vehicle) and the total neurons to 84.9 +/- 6.6 (p = 0.046 vs. 3xTgAD vehicle) of non-Tg mice. These findings indicate that there is a loss of neurons, specifically the TH positive neurons in SNpc of 3xTgAD mice, and that AP alpha reverses the lesion in SNpc of 3xTgAD by increasing the formation of new TH neurons.

• 出版日期2012-5