PMID- 29357673
OWN - NLM
STAT- MEDLINE
DCOM- 20190930
LR  - 20190930
IS  - 1557-7716 (Electronic)
IS  - 1523-0864 (Linking)
VI  - 29
IP  - 12
DP  - 2018 Oct 20
TI  - Calcium Release Mediated by Redox-Sensitive RyR2 Channels Has a Central Role in 
      Hippocampal Structural Plasticity and Spatial Memory.
PG  - 1125-1146
LID - 10.1089/ars.2017.7277 [doi]
AB  - AIMS: Previous studies indicate that hippocampal synaptic plasticity and spatial 
      memory processes entail calcium release from intracellular stores mediated by 
      ryanodine receptor (RyR) channels. In particular, RyR-mediated Ca(2+) release is 
      central for the dendritic spine remodeling induced by brain-derived neurotrophic 
      factor (BDNF), a neurotrophin that stimulates complex signaling pathways leading 
      to memory-associated protein synthesis and structural plasticity. To examine if 
      upregulation of ryanodine receptor type-2 (RyR2) channels and the spine 
      remodeling induced by BDNF entail reactive oxygen species (ROS) generation, and 
      to test if RyR2 downregulation affects BDNF-induced spine remodeling and spatial 
      memory. RESULTS: Downregulation of RyR2 expression (short hairpin RNA [shRNA]) in 
      primary hippocampal neurons, or inhibition of nitric oxide synthase (NOS) or 
      NADPH oxidase, prevented agonist-mediated RyR-mediated Ca(2+) release, whereas 
      BDNF promoted cytoplasmic ROS generation. RyR2 downregulation or inhibitors of 
      N-methyl-d-aspartate (NMDA) receptors, or NOS or of NADPH oxidase type-2 (NOX2) 
      prevented RyR2 upregulation and the spine remodeling induced by BDNF, as did 
      incubation with the antioxidant agent N-acetyl l-cysteine. In addition, 
      intrahippocampal injection of RyR2-directed antisense oligodeoxynucleotides, 
      which caused significant RyR2 downregulation, caused conspicuous defects in a 
      memorized spatial memory task. INNOVATION: The present novel results emphasize 
      the key role of redox-sensitive Ca(2+) release mediated by RyR2 channels for 
      hippocampal structural plasticity and spatial memory. CONCLUSION: Based on these 
      combined results, we propose (i) that BDNF-induced RyR2-mediated Ca(2+) release 
      and ROS generation via NOS/NOX2 are strictly required for the dendritic spine 
      remodeling and the RyR2 upregulation induced by BDNF, and (ii) that RyR2 channel 
      expression is crucial for spatial memory processes. Antioxid. Redox Signal. 29, 
      1125-1146.
FAU - More, Jamileth Y
AU  - More JY
AD  - 1 Biomedical Neuroscience Institute , Faculty of Medicine, Universidad de Chile, 
      Santiago, Chile .
FAU - Bruna, Barbara A
AU  - Bruna BA
AD  - 1 Biomedical Neuroscience Institute , Faculty of Medicine, Universidad de Chile, 
      Santiago, Chile .
FAU - Lobos, Pedro E
AU  - Lobos PE
AD  - 1 Biomedical Neuroscience Institute , Faculty of Medicine, Universidad de Chile, 
      Santiago, Chile .
FAU - Galaz, Jose L
AU  - Galaz JL
AD  - 1 Biomedical Neuroscience Institute , Faculty of Medicine, Universidad de Chile, 
      Santiago, Chile .
FAU - Figueroa, Paula L
AU  - Figueroa PL
AD  - 1 Biomedical Neuroscience Institute , Faculty of Medicine, Universidad de Chile, 
      Santiago, Chile .
FAU - Namias, Silvia
AU  - Namias S
AD  - 1 Biomedical Neuroscience Institute , Faculty of Medicine, Universidad de Chile, 
      Santiago, Chile .
FAU - Sanchez, Gina L
AU  - Sanchez GL
AD  - 2 Institute of Biomedical Sciences, Faculty of Medicine, Universidad de Chile, 
      Santiago, Chile .
FAU - Barrientos, Genaro C
AU  - Barrientos GC
AD  - 2 Institute of Biomedical Sciences, Faculty of Medicine, Universidad de Chile, 
      Santiago, Chile .
FAU - Valdes, Jose L
AU  - Valdes JL
AD  - 1 Biomedical Neuroscience Institute , Faculty of Medicine, Universidad de Chile, 
      Santiago, Chile .
AD  - 3 Department of Neuroscience, Faculty of Medicine, Universidad de Chile , 
      Santiago, Chile .
FAU - Paula-Lima, Andrea C
AU  - Paula-Lima AC
AD  - 1 Biomedical Neuroscience Institute , Faculty of Medicine, Universidad de Chile, 
      Santiago, Chile .
AD  - 4 Institute for Research in Dental Sciences, Faculty of Medicine, Universidad de 
      Chile, Santiago, Chile .
FAU - Hidalgo, Cecilia
AU  - Hidalgo C
AD  - 1 Biomedical Neuroscience Institute , Faculty of Medicine, Universidad de Chile, 
      Santiago, Chile .
AD  - 2 Institute of Biomedical Sciences, Faculty of Medicine, Universidad de Chile, 
      Santiago, Chile .
AD  - 3 Department of Neuroscience, Faculty of Medicine, Universidad de Chile , 
      Santiago, Chile .
AD  - 5 Center for Exercise , Metabolism and Cancer Studies, Faculty of Medicine, 
      Universidad de Chile, Santiago, Chile .
FAU - Adasme, Tatiana
AU  - Adasme T
AD  - 1 Biomedical Neuroscience Institute , Faculty of Medicine, Universidad de Chile, 
      Santiago, Chile .
AD  - 6 Centro Integrativo de Biologia y Quimica Aplicada, Universidad Bernardo 
      O'Higgins , Santiago, Chile .
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180301
PL  - United States
TA  - Antioxid Redox Signal
JT  - Antioxidants & redox signaling
JID - 100888899
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (RyR2 protein, rat)
RN  - 0 (Ryanodine Receptor Calcium Release Channel)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Animals
MH  - Calcium/*metabolism
MH  - Cells, Cultured
MH  - Hippocampus/cytology/*metabolism
MH  - *Neuronal Plasticity
MH  - Oxidation-Reduction
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Reactive Oxygen Species/metabolism
MH  - Ryanodine Receptor Calcium Release Channel/*metabolism
MH  - *Spatial Memory
OTO - NOTNLM
OT  - BDNF
OT  - Ca2+ signals
OT  - NADPH oxidase
OT  - dendritic spines
OT  - reactive oxygen species
OT  - spatial memory training
EDAT- 2018/01/24 06:00
MHDA- 2019/10/01 06:00
CRDT- 2018/01/24 06:00
PHST- 2018/01/24 06:00 [pubmed]
PHST- 2019/10/01 06:00 [medline]
PHST- 2018/01/24 06:00 [entrez]
AID - 10.1089/ars.2017.7277 [doi]
PST - ppublish
SO  - Antioxid Redox Signal. 2018 Oct 20;29(12):1125-1146. doi: 10.1089/ars.2017.7277. 
      Epub 2018 Mar 1.