PMID- 19533679
OWN - NLM
STAT- MEDLINE
DCOM- 20100810
LR  - 20191210
IS  - 1098-1063 (Electronic)
IS  - 1050-9631 (Linking)
VI  - 20
IP  - 5
DP  - 2010 May
TI  - Beta-adrenergic receptors link NO/sGC/PKG signaling to BDNF expression during the 
      consolidation of object recognition long-term memory.
PG  - 672-83
LID - 10.1002/hipo.20656 [doi]
AB  - The nitric oxide (NO)/soluble guanylyl cyclase (sGC)/protein kinase G (PKG) 
      pathway is important for memory processing, but the identity of its downstream 
      effectors as well as its actual participation in the consolidation of nonaversive 
      declarative long-term memory (LTM) remain unknown. Here, we show that training 
      rats in an object recognition (OR) learning task rapidly increased 
      nitrites/nitrates (NOx) content in the CA1 region of the dorsal hippocampus while 
      posttraining intra-CA1 microinfusion of the neuronal NO synthase (nNOS) inhibitor 
      L-NN hindered OR LTM retention without affecting memory retrieval or other 
      behavioral variables. The amnesic effect of L-NN was not state dependent, was 
      mimicked by the sGC inhibitor LY83583 and the PKG inhibitor KT-5823, and reversed 
      by coinfusion of the NO donor S-nitroso-N-acetylpenicillamine (SNAP) and the PKG 
      activator 8-bromoguanosine 3',5'-cyclic monophosphate (8Br-cGMP). SNAP did not 
      affect the amnesic effect of LY83583 and KT-5823. Conversely, 8Br-cGMP overturned 
      the amnesia induced by LY83583 but not that caused by KT-5823. Intra-CA1 infusion 
      of the beta-adrenergic receptor blocker timolol right after training hindered OR 
      LTM and, although coadministration of noradrenaline reversed the amnesia caused 
      by L-NN, LY83583, and KT5823, the amnesic effect of timolol was unaffected by 
      coinfusion of 8Br-cGMP or SNAP, indicating that hippocampal beta-adrenergic 
      receptors act downstream NO/sGC/PKG signaling. We also found that posttraining 
      intra-CA1 infusion of function-blocking anti-brain-derived neurotrophic factor 
      (BDNF) antibodies hampered OR LTM retention, whereas OR training increased CA1 
      BDNF levels in a nNOS- and beta-adrenergic receptor-dependent manner. Taken 
      together, our results demonstrate that NO/sGC/PKG signaling in the hippocampus is 
      essential for OR memory consolidation and suggest that beta-adrenergic receptors 
      link the activation of this pathway to BDNF expression during the consolidation 
      of declarative memories.
CI  - 2009 Wiley-Liss, Inc.
FAU - Furini, Cristiane R
AU  - Furini CR
AD  - Centro de Memoria, Instituto do Cerebro, Pontificia Universidade Catolica do Rio 
      Grande do Sul and Instituto Nacional de Neurociencia Translacional, Conselho 
      Nacional de Desenvolvimento Cientifico e Tecnologico, Porto Alegre, RS, Brasil.
FAU - Rossato, Janine I
AU  - Rossato JI
FAU - Bitencourt, Lucas L
AU  - Bitencourt LL
FAU - Medina, Jorge H
AU  - Medina JH
FAU - Izquierdo, Ivan
AU  - Izquierdo I
FAU - Cammarota, Martin
AU  - Cammarota M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Hippocampus
JT  - Hippocampus
JID - 9108167
RN  - 0 (Adrenergic beta-Antagonists)
RN  - 0 (Antibodies)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Receptors, Adrenergic, beta)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - 817W3C6175 (Timolol)
RN  - EC 2.7.11.12 (Cyclic GMP-Dependent Protein Kinases)
RN  - EC 4.6.1.2 (Guanylate Cyclase)
SB  - IM
MH  - Adrenergic beta-Antagonists/pharmacology
MH  - Animals
MH  - Antibodies/pharmacology
MH  - Behavior, Animal
MH  - Brain-Derived Neurotrophic Factor/immunology/*metabolism
MH  - Cyclic GMP-Dependent Protein Kinases/metabolism
MH  - Discrimination Learning/physiology
MH  - Dose-Response Relationship, Drug
MH  - Drug Interactions
MH  - Enzyme Inhibitors/pharmacology
MH  - Gene Expression Regulation/drug effects/*physiology
MH  - Guanylate Cyclase/metabolism
MH  - Male
MH  - Nitric Oxide/metabolism
MH  - Rats
MH  - Rats, Wistar
MH  - Receptors, Adrenergic, beta/*physiology
MH  - Recognition, Psychology/drug effects/*physiology
MH  - Signal Transduction/drug effects/*physiology
MH  - Time Factors
MH  - Timolol/pharmacology
EDAT- 2009/06/18 09:00
MHDA- 2010/08/11 06:00
CRDT- 2009/06/18 09:00
PHST- 2009/06/18 09:00 [entrez]
PHST- 2009/06/18 09:00 [pubmed]
PHST- 2010/08/11 06:00 [medline]
AID - 10.1002/hipo.20656 [doi]
PST - ppublish
SO  - Hippocampus. 2010 May;20(5):672-83. doi: 10.1002/hipo.20656.