PMID- 24072674
OWN - NLM
STAT- MEDLINE
DCOM- 20140521
LR  - 20220408
IS  - 1573-6903 (Electronic)
IS  - 0364-3190 (Linking)
VI  - 38
IP  - 11
DP  - 2013 Nov
TI  - Class I histone deacetylase inhibitor valproic acid reverses cognitive deficits 
      in a mouse model of septic encephalopathy.
PG  - 2440-9
LID - 10.1007/s11064-013-1159-0 [doi]
AB  - Accumulating evidence suggests that histone deacetylase inhibitor exert 
      neuroprotective effects in animal models of neurological diseases. We 
      investigated for the first time whether class I histone deacetylase inhibitor 
      valproic acid (VPA) can reverse cognitive deficits in a mouse model of 
      sepsis-associated encephalopathy (SAE). Moreover, the possible mechanisms of 
      protection were also explored. A mouse model of SAE was induced in adult male 
      mice by cecal ligation and puncture (CLP). Mice received an administration of 
      saline or VPA (100 mg/kg) once daily for 14 consecutive days starting either 
      immediately or 2 weeks after operation. Furthermore, the TrkB antagonist K252a 
      was used in another group of experiment to investigate whether brain-derived 
      neurotrophic factor (BDNF)-TrkB signaling pathway is involved in the protection 
      of VPA. Our data suggested that CLP resulted in significant cognitive impairments 
      accompanied by increased expressions in interleukin-1beta and caspase-3, and 
      decreased expressions in BDNF, phospho-TrkB (pTrkB), postsynaptic density 95, and 
      synapses, which were reversed by VPA. However, TrkB antagonist K252a abolished 
      the beneficial effects of VPA with regard to cognition and decreased pTrkB 
      expression and synapses in the hippocampus. Taken together, the findings of the 
      present study suggested chronic treatment with VPA reverses cognitive deficits 
      through mechanisms probably via a reduction in inflammation and apoptosis in the 
      brain, as well as the activation of the BDNF-TrkB signaling pathway in a mouse 
      model of SAE.
FAU - Wu, Jing
AU  - Wu J
AD  - Department of Anesthesiology, Jinling Hospital, 305 East Zhongshan Road, Nanjing, 
      China.
FAU - Dong, Lin
AU  - Dong L
FAU - Zhang, Mingqiang
AU  - Zhang M
FAU - Jia, Min
AU  - Jia M
FAU - Zhang, Guangfeng
AU  - Zhang G
FAU - Qiu, Lili
AU  - Qiu L
FAU - Ji, Muhuo
AU  - Ji M
FAU - Yang, Jianjun
AU  - Yang J
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130926
PL  - United States
TA  - Neurochem Res
JT  - Neurochemical research
JID - 7613461
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Carbazoles)
RN  - 0 (Histone Deacetylase Inhibitors)
RN  - 0 (Indole Alkaloids)
RN  - 0 (Neuroprotective Agents)
RN  - 614OI1Z5WI (Valproic Acid)
RN  - 97161-97-2 (staurosporine aglycone)
RN  - EC 2.7.10.1 (Receptor, trkB)
SB  - IM
MH  - Animals
MH  - Brain Diseases/complications
MH  - Brain-Derived Neurotrophic Factor/physiology
MH  - Carbazoles/pharmacology
MH  - Cecum/surgery
MH  - Cognition Disorders/etiology/*prevention & control
MH  - Disease Models, Animal
MH  - Histone Deacetylase Inhibitors/*pharmacology
MH  - Indole Alkaloids/pharmacology
MH  - Ligation
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Neuroprotective Agents/pharmacology
MH  - Punctures
MH  - Receptor, trkB/antagonists & inhibitors/physiology
MH  - Sepsis/complications
MH  - Signal Transduction/drug effects
MH  - Valproic Acid/*pharmacology
EDAT- 2013/09/28 06:00
MHDA- 2014/05/23 06:00
CRDT- 2013/09/28 06:00
PHST- 2013/07/04 00:00 [received]
PHST- 2013/09/18 00:00 [accepted]
PHST- 2013/09/15 00:00 [revised]
PHST- 2013/09/28 06:00 [entrez]
PHST- 2013/09/28 06:00 [pubmed]
PHST- 2014/05/23 06:00 [medline]
AID - 10.1007/s11064-013-1159-0 [doi]
PST - ppublish
SO  - Neurochem Res. 2013 Nov;38(11):2440-9. doi: 10.1007/s11064-013-1159-0. Epub 2013 
      Sep 26.