MK4MDD

Genetic/Epigenetic Locus Search Cross Data Search

Study Report

Reference

Citation	Qi X, 2009 PubMed
Full Info	Qi X, Lin W, Wang D, Pan Y, Wang W, Sun M. A role for the extracellular signal-regulated kinase signal pathway in depressive-like behavior. Behav Brain Res 2009; 199(2): 203-209.

Study

Hypothesis or Background	Our recent research demonstrates that the extracellular signal-regulated kinase (ERK) signal pathway is impaired in depressed animals, and such disruption is effectively reversed following antidepressant treatment. These results indicate that the ERK pathway may participate in the molecular mechanism of depression. To provide direct evidence for the potential role of the ERK pathway in depression, the present study using a sub-chronic regimen of ERK inhibition investigated the disparate role for the ERK cascade in two specific brain areas, the dorsal hippocampus (dHP) and the medial prefrontal cortex (mPFC), in the pathophysiology of depressive-like behavior.
Sample Information	rat
Method Detail	Rats were bilaterally implanted with cannulas in the dHP or mPFC and were microinjected with U0126, a specific inhibitor of ERK upstream activator, or vehicle for 7 consecutive days. The behavioral effects of the ERK pathway inhibition were examined in the open field, elevated plus maze, and saccharin preference test.
Method Keywords	dose administration; open field test; elevated plus maze; sucrose preference test
Result	The results showed that the inhibition of the ERK pathway in dHP resulted in anhedonia and anxiety-like behavior, and the ERK pathway inhibition in the mPFC induced anhedonia and locomotor impairment in rats. The phosphorylation of the cyclic AMP-responsive-element-binding protein (CREB) was decreased following the ERK pathway inhibition either in dHP or mPFC.
Conclusions	These findings demonstrate that the ERK pathway in either the dHP or mPFC participates in the pathophysiology of the depressive-like behavior, and may have pivotal role in human

Relationships reported by Qi X, 2009

Component A Approved Name (Name in Paper)	Component A Type	Component B Approved Name (Name in Paper)	Component B Type	Statistical Result	Relationship Description	Result Category (Positive/Negative))
Anxiety-like behaviors from animal model (anxiety-like behavior)	cognition and behavior	mapkkk cascade (ERK pathway)	pathway		The inhibition of the ERK pathway in dHP resulted in anhedonia and anxiety-like behavior, and the ERK pathway inhibition in the mPFC induced anhedonia and locomotor impairment in rats	Positive
anhedonic-like behavior from animal model (anhedonic-like behavior)	cognition and behavior	mapkkk cascade (ERK pathway)	pathway		The inhibition of the ERK pathway in dHP resulted in anhedonia and anxiety-like behavior, and the ERK pathway inhibition in the mPFC induced anhedonia and locomotor impairment in rats	Positive
Irritability (increased irritability)	symptoms	mapkkk cascade (ERK pathway)	pathway		The inhibition of the ERK pathway in dHP resulted in anhedonia and anxiety-like behavior, and the ERK pathway inhibition in the mPFC induced anhedonia and locomotor impairment in rats	Positive
U0126 (U0126)	molecule	mapkkk cascade (ERK pathway)	pathway		U0126, a specific inhibitor of ERK upstream activator	Positive
mapkkk cascade (ERK pathway)	pathway	Cyclic AMP-responsive element-binding protein 1 (cAMP response element-binding protein (CREB))	protein		The phosphorylation of the cyclic AMP-responsive-element-binding protein (CREB) was decreased following the ERK pathway inhibition	Positive
anhedonic-like behavior from animal model (anhedonic-like behavior)	cognition and behavior	Fronto-parietal connection (frontal cortex)	brain morphology and function		The ERK pathway inhibition in the medial prefrontal cortex induced anhedonia and locomotor impairment in rats	Positive
anhedonic-like behavior from animal model (anhedonic-like behavior)	cognition and behavior	Hippocampus (hippocampus)	brain morphology and function		The inhibition of the ERK pathway in dorsal hippocampus resulted in anhedonia and anxiety-like behavior	Positive
Anxiety-like behaviors from animal model (anxiety-like behavior)	cognition and behavior	Hippocampus (hippocampus)	brain morphology and function		The inhibition of the ERK pathway in dorsal hippocampus resulted in anhedonia and anxiety-like behavior	Positive
Irritability (increased irritability)	symptoms	Hippocampus (hippocampus)	brain morphology and function		The inhibition of the ERK pathway in dorsal hippocampus resulted in anhedonia and anxiety-like behavior	Positive