PMID- 25881985
OWN - NLM
STAT- MEDLINE
DCOM- 20160216
LR  - 20150527
IS  - 1532-2777 (Electronic)
IS  - 0306-9877 (Linking)
VI  - 85
IP  - 1
DP  - 2015 Jul
TI  - Activation of NMDA receptor by elevated homocysteine in chronic liver disease 
      contributes to encephalopathy.
PG  - 64-7
LID - S0306-9877(15)00142-5 [pii]
LID - 10.1016/j.mehy.2015.03.027 [doi]
AB  - Liver diseases lead to a complex syndrome characterized by neurological, 
      neuro-psychiatric and motor complications, called hepatic encephalopathy, which 
      is prevalent in patients and animal models of acute, sub-chronic and chronic 
      liver failure. Although alterations in GABAergic, glutamatergic, cholinergic and 
      serotonergic neuronal functions have been implicated in HE, the molecular 
      mechanisms that lead to HE in chronic liver disease (CLD) is least illustrated. 
      Due to hepatocellular failure, levels of ammonia and homocysteine (Hcy), in 
      addition to others, are found to increase in the brain as well as plasma. Hcy, a 
      non-protein forming amino acid and an excitotoxin, activates ionotropic glutamate 
      (n-methyl-d-aspartate; NMDA) receptors, and thereby leads to influx of Ca(2+) 
      into neurons, which in turn activates several pathways that trigger oxidative 
      stress, inflammation and apoptosis, collectively called excitotoxicity. Elevated 
      levels of Hcy in the plasma and brain, a condition called Hyperhomocysteinemia 
      (HHcy), and the resultant NMDA receptor-mediated excitotoxicity has been 
      implicated in several diseases, including Parkinson's disease and Alzheimer's 
      disease. Although, hyperammonemia has been shown to cause excitotoxicity, the 
      role of HHcy in the development of behavioral and neurochemical alterations that 
      occur in HE has not been illustrated yet. It is hypothesized that CLD-induced 
      HHcy plays a major role in the development of HE through activation of NMDA 
      receptors. It is further hypothesized that HHcy synergizes with hyperammonemia to 
      activate NMDA receptor in the brain, and thereby cause oxidative stress, 
      inflammation and apoptosis, and neuronal loss that leads to HE.
CI  - Copyright (c) 2015 Elsevier Ltd. All rights reserved.
FAU - Choudhury, Sabanum
AU  - Choudhury S
AD  - Cellular and Molecular Neurobiology Laboratory, Department of Life Science and 
      Bioinformatics, Assam University, Silchar 788011, Assam, India.
FAU - Borah, Anupom
AU  - Borah A
AD  - Cellular and Molecular Neurobiology Laboratory, Department of Life Science and 
      Bioinformatics, Assam University, Silchar 788011, Assam, India. Electronic 
      address: anupomborahh@gmail.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150403
PL  - United States
TA  - Med Hypotheses
JT  - Medical hypotheses
JID - 7505668
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
RN  - 0LVT1QZ0BA (Homocysteine)
SB  - IM
MH  - Brain Diseases/*metabolism
MH  - Chronic Disease
MH  - Homocysteine/*metabolism
MH  - Humans
MH  - Liver Diseases/*metabolism
MH  - Receptors, N-Methyl-D-Aspartate/*metabolism
EDAT- 2015/04/18 06:00
MHDA- 2016/02/18 06:00
CRDT- 2015/04/18 06:00
PHST- 2015/01/23 00:00 [received]
PHST- 2015/03/23 00:00 [revised]
PHST- 2015/03/28 00:00 [accepted]
PHST- 2015/04/18 06:00 [entrez]
PHST- 2015/04/18 06:00 [pubmed]
PHST- 2016/02/18 06:00 [medline]
AID - S0306-9877(15)00142-5 [pii]
AID - 10.1016/j.mehy.2015.03.027 [doi]
PST - ppublish
SO  - Med Hypotheses. 2015 Jul;85(1):64-7. doi: 10.1016/j.mehy.2015.03.027. Epub 2015 
      Apr 3.