PKC activation during training restores mushroom spine synapses and memory in the aged rat
PKC activation during training restores mushroom spine synapses and memory in the aged rat
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DOI：
10.1016/j.nbd.2013.03.012
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发表时间：
2013-07-01
影响因子：
6.1
通讯作者：
Alkon, Daniel L.
中科院分区：
文献类型：
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作者：
Hongpaisan, Jarin;Xu, Changqing;Alkon, Daniel L.
蛋白激酶C（PKC）α和α激活与突触发生有关。我们使用老年大鼠来测试PKC β/α激活剂blyostatin和PKC ε特异性激活剂DCP-LA结合空间记忆训练是否可以恢复蘑菇树突棘发生和突触发生。与年轻大鼠相比，老年学习障碍大鼠的记忆保持能力较低; CA 1锥体神经元顶树突中蘑菇棘和突触的密度较低;含有PKC ε的突触前轴突终扣较少;两种PKC β/α底物，mRNA稳定蛋白HuD和脑源性神经营养因子（BDNF）的活化和表达较低。PKC激活剂治疗与空间记忆训练相结合，恢复了蘑菇棘和蘑菇棘突触;挽救了PKC β/α表达和PKC/HuD/BDNF信号传导;并将记忆恢复到年轻大鼠的水平。这些作用是通过用苔藓抑素或PKC ε特异性激活剂DCP-LA治疗产生的。苔藓抑素还逆转了老年学习障碍大鼠GABA能抑制性突触后电流（IPSPs）的改变。因此，我们的研究结果支持PKC激活剂的治疗潜力时，添加到认知康复诱导蘑菇棘突触和逆转与衰老相关的记忆衰退。(c)2013 Elsevier Inc. All rights reserved.
Protein kinase C (PKC) epsilon and alpha activation has been implicated in synaptogenesis. We used aged rats to test whether the PKC epsilon/alpha activator blyostatin and PKC epsilon-specific activator DCP-LA combined with spatial memory training could restore mushroom dendritic spinogenesis and synaptogenesis. Compared with young rats, aged, learning-impaired rats had lower memory retention; lower densities of mushroom spines and synapses in the apical dendrites of CA1 pyramidal neurons; fewer PKC epsilon-containing presynaptic axonal boutons; and lower activation and expression of two PKC epsilon/alpha substrates, the mRNA-stabilizing protein HuD and brain-derived neurotrophic factor (BDNF). PKC activator treatment combined with spatial memory training restored mushroom spines and mushroom spine synapses; rescued PKC epsilon/alpha expression and PKC/HuD/BDNF signaling; and normalized memory to the levels seen in young rats. These effects were produced by treatment with either bryostatin or the PKC epsilon-specific activator, DCP-LA. Bryostatin also reversed alterations in GABAergic inhibitory postsynaptic currents (IPSPs) in aged, learning-impaired rats. Thus, our results support the therapeutic potential of PKC activators when added to cognitive rehabilitation for inducing mushroom spine synaptogenesis and reversing memory decline associated with aging. (c) 2013 Elsevier Inc. All rights reserved.