School of Clinical Sciences, Faculty of Medicine and Dentistry, University of Bristol, Bristol, UK.
Department of Oriental Pharmaceutical Science, College of Pharmacy, Kyung Hee University, Seoul, Republic of Korea.
Mol Neurobiol. 2018 Sep;55(9):7453-7462. doi: 10.1007/s12035-018-0919-x. Epub 2018 Feb 9.
Understanding the mechanisms underlying the natural decay of long-term memory can help us find means of extending the duration of long-term memory. However, the neurobiological processes involved in the decay of long-term memory are poorly understood. In the present study, we examined the effect of acute and chronic treatment of fluoxetine on natural decay of long-term memory and the possible mechanism. Late administration of fluoxetine prolonged the persistence of long-term memory in mice, as demonstrated by object location recognition and Barnes maze tests. Fluoxetine altered Akt/glycogen synthase kinase-3β (GSK-3β)/β-catenin signaling in the hippocampus. Late short- and long-term pharmacological inhibition of GSK-3β mimicked the effect of fluoxetine on memory persistence. Pharmacological inhibition of Akt blocked the effect of fluoxetine on memory persistence. Finally, late infusion of fluoxetine increased hippocampal long-term potentiation (LTP) and pharmacological inhibition of GSK-3β blocked the natural decline in LTP. These results demonstrate that GSK-3β might be a key molecule in memory decay process, and fluoxetine extends the period of long-term memory maintenance via Akt/GSK-3β signaling.
了解长期记忆自然衰减的机制可以帮助我们找到延长长期记忆持续时间的方法。然而，长期记忆衰减所涉及的神经生物学过程还知之甚少。在本研究中，我们研究了氟西汀的急性和慢性治疗对长期记忆自然衰减的影响及其可能的机制。结果表明，氟西汀的晚期给药延长了小鼠的长期记忆持续时间，这通过物体位置识别和 Barnes 迷宫测试得到了证明。氟西汀改变了海马中的 Akt/糖原合酶激酶-3β（GSK-3β）/β-连环蛋白信号通路。GSK-3β 的短期和长期药理学抑制模拟了氟西汀对记忆持续时间的影响。Akt 的药理学抑制阻断了氟西汀对记忆持续时间的影响。最后，氟西汀的晚期输注增加了海马长时程增强（LTP），而 GSK-3β 的药理学抑制阻断了 LTP 的自然下降。这些结果表明，GSK-3β 可能是记忆衰减过程中的关键分子，而氟西汀通过 Akt/GSK-3β 信号通路延长了长期记忆的维持时间。
