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

Neurobiology of Disease

Changqing Xu¹  Thomas J. Nelson²  Daniel L. Alkon²  Abhik Sen²  Jarin Hongpaisan³ 

[1] Blanchette Rockefeller Neurosciences Institute at West Virginia University, Morgantown, WV, 26505, USA;Blanchette Rockefeller Neurosciences Institute at West Virginia University, Morgantown, WV, 26505, USA;Corresponding author at: Blanchette Rockefeller Neurosciences Institute, 8 Medical Center Drive, Morgantown, WV 26505-3409, USA. Fax: [phone].;

关键词: Aging;    PKC;    Synapse;    Dendritic spine;    Hippocampus;   

DOI  :  

来源: DOAJ

【 摘 要 】

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

【 授权许可】

Unknown