14-3-3η as a promising target for the treatment of Major Depression Disorder

Major depressive disorder (MDD) is the second largest contributing factor to disability in developed countries. Serotonergic or adrenergic-based antidepressants require 2-4 weeks of use before relief of symptoms occur. This lag time, unfortunately, presents a vulnerability to suicide. Clinical studies show that ketamine acts rapidly and is efficacious in treating depression. However, ketamine has the potential for abuse, tempering enthusiasm for its use. Thus developing new antidepressants that act rapidly and have less side-effect is vital.

Recent studies suggest that rapid antidepressants cause a shift in the g-aminobutyric acid receptor (GABA_BR) signaling pathway, such that GABA_BR activation shifts from opening inwardly rectifying potassium channels (Kir/GIRK) to increase resting dendritic calcium signal and mammalian Target of Rapamycin activity. Nevertheless, little is known about the molecular and biochemical mechanisms that initiate this shift. Herein, Workman et al. figure out that GABA_BR signaling to Kir3 (GIRK) channels decreases with NMDAR blockade. Blocking NMADR signaling stabilizes the adaptor protein 14-3-3h, which decouples GABA_BR signaling from Kir3 which is required for the rapid antidepressants efficacy. Moreover, GABA_BR and 14-3-3h levels decrease in the hippocampus of socially defeated rodents, a model for depression. Treatment with NMDAR antagonists increases GABA_BR and 14-3-3h expression while decreases Kir3.2 level in these neurons. Taken together, this study support a central role for 14-3-3h in the efficacy of rapid antidepressants and define a critical molecular mechanism for activity-dependent alterations in GABA_BR signaling.

g-aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the brain. GABA levels have been reported to be low in the plasma samples of MDD patients. arigo provides GABA ELISA kit (ARG80451) for researchers to demonstrate the relationship between GABA secretion and depression. 14-3-3 proteins are a family of conserved regulatory molecules that have the ability to bind to many functionally diverse signaling molecules including kinases, phosphatases and receptors. arigo provides 14-3-3 Family Antibody Panel (ARG30116) for the study of 14-3-3 protein functions. MAP2, Tau and Nestin are common neuronal markers used in neuroscience studies. Neuron Marker Antibody Duo (ARG30009) and Neuron Development Marker Antibody Duo (ARG30083) are the best options for elucidating neuronal patterns in your immunostaining experiments.

Antibody Duo

 

Neuron Marker Antibody Duo (ARG30009)
	ARG52328 MAP2 Antibody		ARG52345 Nestin Antibody
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Neuron Development Marker Antibody Duo (ARG30083)
	ARG52441 Tau Antibody		ARG53358 Nestin Antibody

 

 

Antibody Panel

 

14-3-3 Family Antibody Panel (ARG30116)
	ARG64363 14-3-3 tau Antibody		ARG52473 14-3-3 beta Antibody
	ARG51169 14-3-3 zeta Antibody		ARG63881 14-3-3 sigma Antibody

 

 

ELISA Kit

 

	ARG80451 GABA ELISA Kit