PMID- 29561292
OWN - NLM
STAT- MEDLINE
DCOM- 20190731
LR  - 20190731
IS  - 1473-5849 (Electronic)
IS  - 0955-8810 (Linking)
VI  - 29
IP  - 5
DP  - 2018 Aug
TI  - Behavioral effects of toll-like receptor-4 antagonist 'eritoran' in an 
      experimental model of depression: role of prefrontal and hippocampal neurogenesis 
      and gamma-aminobutyric acid/glutamate balance.
PG  - 413-425
LID - 10.1097/FBP.0000000000000390 [doi]
AB  - Depression is the disease of the modern era. The lack of response to the 
      available antidepressants, which were developed on the basis of the monoaminergic 
      deficit hypothesis of depression, has encouraged scientists to think about new 
      mechanisms explaining the pathogenesis of depression. In this context, the 
      inflammatory theory has emerged to clarify many aspects of depression that the 
      previous theories have failed to explain. Toll-like receptor-4 (TLR-4) has a 
      regulatory role in the brain's immune response to stress, and its activation is 
      suggested to play a pivotal role in the pathophysiology of depression. In this 
      study, we tested eritoran (ERI), a TLR-4 receptor-4 antagonist, as a potential 
      antidepressant. We investigated the effect of long-term administration of ERI in 
      three different doses on behavioral changes, hippocampal and prefrontal cortex 
      (PFC) neurogenesis, and gamma-aminobutyric acid (GABA)/glutamate balance in male 
      Wistar rats exposed to chronic restraint stress (CRS). Long-term administration 
      of ERI ameliorated CRS-induced depressive-like symptoms and 
      hypothalamic-pituitary-adrenal axis hyperactivity alongside reducing levels of 
      hippocampal and PFC inflammatory cytokines, restoring GABA and glutamate balance, 
      and enhancing PFC and hippocampal neurogenesis, by increasing BDNF gene and 
      protein expression in a dose-dependent manner. The results demonstrate an 
      antidepressant-like activity of ERI in Wistar rats exposed to CRS, which may be 
      largely mediated by its ability to reduce neuroinflammation, increase BDNF, and 
      restore GABA/glutamate balance in prefrontal cortex and hippocampus. Nonetheless, 
      further studies are needed to characterize the mechanism of the antidepressant 
      effect of ERI.
FAU - Aboul-Fotouh, Sawsan
AU  - Aboul-Fotouh S
AD  - Department of Pharmacology.
AD  - Department of Pharmacology, Clinical Pharmacology Unit.
FAU - Habib, Mohamed
AU  - Habib M
AD  - Department of Pharmacology.
FAU - Asaad, Tarek
AU  - Asaad T
AD  - Department of Neuropsychiatry.
FAU - Kassim, Samar K
AU  - Kassim SK
AD  - Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, 
      Ain Shams University, Cairo, Egypt.
FAU - Ghanem, Mohamed H
AU  - Ghanem MH
AD  - Department of Neuropsychiatry.
LA  - eng
PT  - Journal Article
PL  - England
TA  - Behav Pharmacol
JT  - Behavioural pharmacology
JID - 9013016
RN  - 0 (Antidepressive Agents)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Disaccharides)
RN  - 0 (Sugar Phosphates)
RN  - 0 (Tlr4 protein, rat)
RN  - 0 (Toll-Like Receptor 4)
RN  - 3KX376GY7L (Glutamic Acid)
RN  - 551541VI0Y (eritoran)
RN  - 56-12-2 (gamma-Aminobutyric Acid)
MH  - Animals
MH  - Antidepressive Agents/pharmacology
MH  - Brain-Derived Neurotrophic Factor/metabolism
MH  - Depression/*drug therapy/etiology
MH  - Depressive Disorder/physiopathology
MH  - Disaccharides/metabolism/*pharmacology
MH  - Disease Models, Animal
MH  - Glutamic Acid/drug effects
MH  - Hippocampus/drug effects
MH  - Hypothalamo-Hypophyseal System/drug effects
MH  - Male
MH  - Neurogenesis/drug effects
MH  - Pituitary-Adrenal System/drug effects
MH  - Prefrontal Cortex/drug effects
MH  - Rats
MH  - Rats, Wistar
MH  - Stress, Psychological/physiopathology
MH  - Sugar Phosphates/metabolism/*pharmacology
MH  - Toll-Like Receptor 4/antagonists & inhibitors/drug effects/metabolism
MH  - gamma-Aminobutyric Acid/drug effects
EDAT- 2018/03/22 06:00
MHDA- 2019/08/01 06:00
CRDT- 2018/03/22 06:00
PHST- 2018/03/22 06:00 [pubmed]
PHST- 2019/08/01 06:00 [medline]
PHST- 2018/03/22 06:00 [entrez]
AID - 10.1097/FBP.0000000000000390 [doi]
PST - ppublish
SO  - Behav Pharmacol. 2018 Aug;29(5):413-425. doi: 10.1097/FBP.0000000000000390.