Department of Physiology and Pharmacology, Hotchkiss Brain Institute, University of Calgary, Calgary T2N 4N1, Canada.
Behav Brain Res. 2012 Feb 14;227(2):319-23. doi: 10.1016/j.bbr.2011.03.012. Epub 2011 Mar 23.
Cellular Prion Protein (PrP(C)) is known to mediate a protective role in several neurological conditions such as ischemia and epilepsy. However, so far, little information is available concerning the role of PrP(C) in psychiatric disorders such as depression. Here, we have used PrP(C) null mice to examine a putative role of PrP(C) in depressive-like states. Prion protein null mice exhibited depressive-like behaviour when compared to wild-type mice in both the Forced Swimming Test (FST) and Tail Suspension Test (TST). The clinical antidepressant drug imipramine and the NMDA receptor antagonist MK-801 reversed the depressive-like behaviour observed for knockout mice in the TST. The present data thus indicate that PrP(C) exerts a critical role in modulating the depressive-like state in mice, reinforcing the notion that PrP(C) might be associated with alterations in mood disorder states, and suggests a possible role of PrP(C) as a potential drug target for treating depressive disorders.
细胞朊蛋白（PrP(C)）已知在几种神经疾病中发挥保护作用，如缺血和癫痫。然而，目前关于 PrP(C) 在精神疾病如抑郁症中的作用的信息还很有限。在这里，我们使用 PrP(C) 敲除小鼠来研究 PrP(C) 在抑郁样状态中的潜在作用。与野生型小鼠相比，Prion 蛋白敲除小鼠在强迫游泳试验（FST）和悬尾试验（TST）中表现出抑郁样行为。临床抗抑郁药丙咪嗪和 NMDA 受体拮抗剂 MK-801 逆转了 TST 中观察到的敲除小鼠的抑郁样行为。因此，本研究数据表明，PrP(C) 在调节小鼠的抑郁样状态中发挥关键作用，这进一步支持了 PrP(C) 可能与情绪障碍状态的改变有关的观点，并提示 PrP(C) 作为治疗抑郁障碍的潜在药物靶点的可能性。
