PMID- 23545166 OWN - NLM STAT- MEDLINE DCOM- 20131209 LR - 20151119 IS - 1095-953X (Electronic) IS - 0969-9961 (Linking) VI - 55 DP - 2013 Jul TI - PKC activation during training restores mushroom spine synapses and memory in the aged rat. PG - 44-62 LID - S0969-9961(13)00100-9 [pii] LID - 10.1016/j.nbd.2013.03.012 [doi] AB - Protein kinase C (PKC) epsilon and alpha activation has been implicated in synaptogenesis. We used aged rats to test whether the PKCepsilon/alpha activator bryostatin and PKCepsilon-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 PKCepsilon-containing presynaptic axonal boutons; and lower activation and expression of two PKCepsilon/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 PKCepsilon/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 PKCepsilon-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. CI - Copyright (c) 2013 Elsevier Inc. All rights reserved. FAU - Hongpaisan, Jarin AU - Hongpaisan J AD - Blanchette Rockefeller Neurosciences Institute at West Virginia University, Morgantown, WV 26505, USA. jhongpaisan@brni.org FAU - Xu, Changqing AU - Xu C FAU - Sen, Abhik AU - Sen A FAU - Nelson, Thomas J AU - Nelson TJ FAU - Alkon, Daniel L AU - Alkon DL LA - eng PT - Journal Article DEP - 20130329 PL - United States TA - Neurobiol Dis JT - Neurobiology of disease JID - 9500169 RN - 0 (8-(2-(2-pentyl-cyclopropylmethyl)cyclopropyl)octanoic acid) RN - 0 (Anesthetics, Local) RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Bryostatins) RN - 0 (Caprylates) RN - 0 (ELAV Proteins) RN - 0 (ELAV-Like Protein 4) RN - 0 (Elavl4 protein, rat) RN - 0 (Enzyme Inhibitors) RN - 21306-56-9 (QX-314) RN - 98PI200987 (Lidocaine) RN - EC 2.7.11.13 (Protein Kinase C) SB - IM MH - *Aging MH - Anesthetics, Local/pharmacology MH - Animals MH - Brain-Derived Neurotrophic Factor/genetics/metabolism MH - Bryostatins/pharmacology MH - Caprylates/pharmacology MH - Dendrites/drug effects/*physiology/ultrastructure MH - ELAV Proteins/genetics/metabolism MH - ELAV-Like Protein 4 MH - Electric Stimulation MH - Enzyme Activation/drug effects MH - Enzyme Inhibitors MH - Gene Expression Regulation/drug effects MH - Hippocampus/*cytology/drug effects MH - In Vitro Techniques MH - Inhibitory Postsynaptic Potentials/drug effects MH - Lidocaine/analogs & derivatives/pharmacology MH - Maze Learning/drug effects/physiology MH - Memory/drug effects/*physiology MH - Patch-Clamp Techniques MH - Protein Kinase C/*metabolism MH - Pyramidal Cells/cytology/drug effects MH - Rats MH - Synapses/drug effects/*physiology MH - Time Factors EDAT- 2013/04/03 06:00 MHDA- 2013/12/16 06:00 CRDT- 2013/04/03 06:00 PHST- 2012/07/17 00:00 [received] PHST- 2013/03/14 00:00 [revised] PHST- 2013/03/19 00:00 [accepted] PHST- 2013/04/03 06:00 [entrez] PHST- 2013/04/03 06:00 [pubmed] PHST- 2013/12/16 06:00 [medline] AID - S0969-9961(13)00100-9 [pii] AID - 10.1016/j.nbd.2013.03.012 [doi] PST - ppublish SO - Neurobiol Dis. 2013 Jul;55:44-62. doi: 10.1016/j.nbd.2013.03.012. Epub 2013 Mar 29.