PMID- 29518527
OWN - NLM
STAT- MEDLINE
DCOM- 20190521
LR  - 20190521
IS  - 1090-2139 (Electronic)
IS  - 0889-1591 (Linking)
VI  - 70
DP  - 2018 May
TI  - Systemic inflammation without gliosis mediates cognitive deficits through 
      impaired BDNF expression in bile duct ligation model of hepatic encephalopathy.
PG  - 214-232
LID - S0889-1591(18)30046-1 [pii]
LID - 10.1016/j.bbi.2018.03.002 [doi]
AB  - Chronic liver disease per se induces neuroinflammation that contributes to 
      cognitive deficits in hepatic encephalopathy (HE). However, the processes by 
      which pro-inflammatory molecules result in cognitive impairment still remains 
      unclear. In the present study, a significant increase in the activity of liver 
      function enzymes viz. alanine transaminase (ALT), aspartate transaminase (AST) 
      and alkaline phosphatase (ALP) was observed along with increase in plasma ammonia 
      levels after four weeks of bile duct ligation (BDL) in rats suggesting 
      hepatocellular damage. A significant increase was observed in mRNA expression of 
      interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha) and monocyte 
      chemoattractant protein-1 (MCP-1) in brain regions and liver of BDL rats. 
      Concomitantly, IL-6, TNF-alpha and MCP-1 protein levels were also increased in brain 
      regions, liver and serum of BDL rats suggesting the involvement of 
      blood-brain-axis in inflammatory response. However, a significant decrease was 
      observed in glial fibrillary acidic protein (GFAP) and ionized calcium-binding 
      adaptor molecule-1 (Iba-1) expression at transcriptional and translation level in 
      brain of BDL rats. Immunohistochemical and flowcytometric analysis revealed 
      reduced number of GFAP-immunopositive astrocytes and Iba1-immunopositive 
      microglia in the brain regions of BDL rats. Further, a significant decline was 
      observed in cognitive functions in BDL rats assessed using Morris water maze and 
      novel object recognition tests. Expression of pro and mature form of brain 
      derived neurotrophic factor (BDNF) and its upstream transcription element showed 
      significant reduction in brain of BDL rats. Taken together, the results of the 
      present study suggest that systemic inflammation and reduced expression of BDNF 
      and its upstream transcription factor plays a key role in cognitive decline in 
      HE.
CI  - Copyright (c) 2018 Elsevier Inc. All rights reserved.
FAU - Dhanda, Saurabh
AU  - Dhanda S
AD  - Department of Biochemistry, Basic Medical Sciences Block-II, Sector-25, Panjab 
      University, Chandigarh 160014, India.
FAU - Gupta, Smriti
AU  - Gupta S
AD  - Department of Biochemistry, Basic Medical Sciences Block-II, Sector-25, Panjab 
      University, Chandigarh 160014, India.
FAU - Halder, Avishek
AU  - Halder A
AD  - Department of Biochemistry, Basic Medical Sciences Block-II, Sector-25, Panjab 
      University, Chandigarh 160014, India.
FAU - Sunkaria, Aditya
AU  - Sunkaria A
AD  - Department of Biochemistry, Basic Medical Sciences Block-II, Sector-25, Panjab 
      University, Chandigarh 160014, India.
FAU - Sandhir, Rajat
AU  - Sandhir R
AD  - Department of Biochemistry, Basic Medical Sciences Block-II, Sector-25, Panjab 
      University, Chandigarh 160014, India. Electronic address: sandhir@pu.ac.in.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180305
PL  - Netherlands
TA  - Brain Behav Immun
JT  - Brain, behavior, and immunity
JID - 8800478
RN  - 0 (Bdnf protein, rat)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Glial Fibrillary Acidic Protein)
RN  - 0 (Interleukin-6)
RN  - 0 (Tumor Necrosis Factor-alpha)
SB  - IM
MH  - Animals
MH  - Astrocytes
MH  - Bile Ducts
MH  - Brain
MH  - Brain-Derived Neurotrophic Factor/genetics/metabolism
MH  - Chemokine CCL2/analysis
MH  - Cholestasis
MH  - Cognition/*physiology
MH  - Cognitive Dysfunction/physiopathology
MH  - Disease Models, Animal
MH  - Glial Fibrillary Acidic Protein/analysis
MH  - Gliosis
MH  - Hepatic Encephalopathy/*immunology/*physiopathology
MH  - Inflammation/physiopathology
MH  - Interleukin-6/analysis
MH  - Ligation
MH  - Liver/metabolism/physiology
MH  - Male
MH  - Microglia
MH  - Rats
MH  - Rats, Wistar
MH  - Tumor Necrosis Factor-alpha/analysis
OTO - NOTNLM
OT  - Bile duct ligation
OT  - Brain derived neurotrophic factor
OT  - Cognitive
OT  - Hepatic Encephalopathy
OT  - Systemic Inflammation
EDAT- 2018/03/09 06:00
MHDA- 2019/05/22 06:00
CRDT- 2018/03/09 06:00
PHST- 2017/06/06 00:00 [received]
PHST- 2018/02/19 00:00 [revised]
PHST- 2018/03/03 00:00 [accepted]
PHST- 2018/03/09 06:00 [pubmed]
PHST- 2019/05/22 06:00 [medline]
PHST- 2018/03/09 06:00 [entrez]
AID - S0889-1591(18)30046-1 [pii]
AID - 10.1016/j.bbi.2018.03.002 [doi]
PST - ppublish
SO  - Brain Behav Immun. 2018 May;70:214-232. doi: 10.1016/j.bbi.2018.03.002. Epub 2018 
      Mar 5.