PKC activation during training restores mushroom spine synapses and memory in the aged rat

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• 作者：Jarin Hongpaisan ; ^{jhongpaisan@brni.org} ; Changqing Xu ; Abhik Sen ; Thomas J. Nelson ; Daniel L. Alkon
• 关键词：Aging ; PKC ; Synapse ; Dendritic spine ; Hippocampus
• 刊名：Neurobiology of Disease
• 出版年：2013
• 出版时间：July, 2013
• 年：2013
• 卷：55
• 期：Complete
• 页码：44-62
• 全文大小：3206 K

文摘

Protein kinase C (PKC) ¦Å and ¦Á activation has been implicated in synaptogenesis. We used aged rats to test whether the PKC¦Å/¦Á activator bryostatin and PKC¦Å-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¦Å-containing presynaptic axonal boutons; and lower activation and expression of two PKC¦Å/¦Á 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¦Å/¦Á 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¦Å-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.