PMID- 23223292
OWN - NLM
STAT- MEDLINE
DCOM- 20130411
LR  - 20220317
IS  - 1529-2401 (Electronic)
IS  - 0270-6474 (Print)
IS  - 0270-6474 (Linking)
VI  - 32
IP  - 49
DP  - 2012 Dec 5
TI  - Brain-derived neurotrophic factor-dependent synaptic plasticity is suppressed by 
      interleukin-1beta via p38 mitogen-activated protein kinase.
PG  - 17714-24
LID - 10.1523/JNEUROSCI.1253-12.2012 [doi]
AB  - Evolving evidence suggests that brain inflammation and the buildup of 
      proinflammatory cytokine increases the risk for cognitive decline and cognitive 
      dysfunction. Interleukin-1beta (IL-1beta), acting via poorly understood mechanisms, 
      appears to be a key cytokine in causing these deleterious effects along with a 
      presumably related loss of long-term potentiation (LTP)-type synaptic plasticity. 
      We hypothesized that IL-1beta disrupts brain-derived neurotrophic factor (BDNF) 
      signaling cascades and thereby impairs the formation of filamentous actin 
      (F-actin) in dendritic spines, an event that is essential for the stabilization 
      of LTP. Actin polymerization in spines requires phosphorylation of the filament 
      severing protein cofilin and is modulated by expression of the immediate early 
      gene product Arc. Using rat organotypic hippocampal cultures, we found that IL-1beta 
      suppressed BDNF-dependent regulation of Arc and phosphorylation of cofilin and 
      cAMP response element-binding protein (CREB), a transcription factor regulating 
      Arc expression. IL-1beta appears to act on BDNF signal transduction by impairing the 
      phosphorylation of insulin receptor substrate 1, a protein that couples 
      activation of the BDNF receptor TrkB to downstream signaling pathways regulating 
      CREB, Arc, and cofilin. IL-1beta upregulated p38 mitogen-activated protein kinase 
      (MAPK), and inhibiting p38 MAPK prevented IL-1beta from disrupting BDNF signaling. 
      IL-1beta also prevented the formation of F-actin in spines and impaired the 
      consolidation, but not the induction, of BDNF-dependent LTP in acute hippocampal 
      slices. The suppressive effect of IL-1beta on F-actin and LTP was prevented by 
      inhibiting p38 MAPK. These findings define a new mechanism for the action of 
      IL-1beta on LTP and point to a potential therapeutic target to restore synaptic 
      plasticity.
FAU - Tong, Liqi
AU  - Tong L
AD  - Institute for Memory Impairments and Neurological Disorders, University of 
      California, Irvine, California 92697, USA.
FAU - Prieto, G Aleph
AU  - Prieto GA
FAU - Kramar, Eniko A
AU  - Kramar EA
FAU - Smith, Erica D
AU  - Smith ED
FAU - Cribbs, David H
AU  - Cribbs DH
FAU - Lynch, Gary
AU  - Lynch G
FAU - Cotman, Carl W
AU  - Cotman CW
LA  - eng
GR  - R01-AG34667/AG/NIA NIH HHS/United States
GR  - MH083346/MH/NIMH NIH HHS/United States
GR  - R01 AG034667/AG/NIA NIH HHS/United States
GR  - P01 AG000538/AG/NIA NIH HHS/United States
GR  - P01-AG000538/AG/NIA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PL  - United States
TA  - J Neurosci
JT  - The Journal of neuroscience : the official journal of the Society for 
      Neuroscience
JID - 8102140
RN  - 0 (Actins)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Cfl1 protein, rat)
RN  - 0 (Cofilin 1)
RN  - 0 (Cyclic AMP Response Element-Binding Protein)
RN  - 0 (Cytoskeletal Proteins)
RN  - 0 (Interleukin-1beta)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (activity regulated cytoskeletal-associated protein)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
SB  - IM
MH  - Actins/metabolism
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/*antagonists & 
      inhibitors/pharmacology/physiology
MH  - Cells, Cultured
MH  - Cerebral Cortex/metabolism/physiology
MH  - Cofilin 1/metabolism
MH  - Cyclic AMP Response Element-Binding Protein/metabolism
MH  - Cytoskeletal Proteins/biosynthesis
MH  - Excitatory Postsynaptic Potentials/drug effects/physiology
MH  - Gene Expression Regulation/physiology
MH  - Hippocampus/physiology
MH  - Interleukin-1beta/pharmacology/*physiology
MH  - Long-Term Potentiation/physiology
MH  - Male
MH  - Mitogen-Activated Protein Kinases/metabolism
MH  - Nerve Tissue Proteins/biosynthesis
MH  - Neuronal Plasticity/*physiology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Signal Transduction/drug effects/physiology
MH  - p38 Mitogen-Activated Protein Kinases/metabolism/*physiology
PMC - PMC3687587
MID - NIHMS427279
EDAT- 2012/12/12 06:00
MHDA- 2013/04/12 06:00
PMCR- 2013/06/05
CRDT- 2012/12/11 06:00
PHST- 2012/12/11 06:00 [entrez]
PHST- 2012/12/12 06:00 [pubmed]
PHST- 2013/04/12 06:00 [medline]
PHST- 2013/06/05 00:00 [pmc-release]
AID - 32/49/17714 [pii]
AID - 3810667 [pii]
AID - 10.1523/JNEUROSCI.1253-12.2012 [doi]
PST - ppublish
SO  - J Neurosci. 2012 Dec 5;32(49):17714-24. doi: 10.1523/JNEUROSCI.1253-12.2012.