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Identification of a novel, fast-acting GABAergic antidepressant

Overview of attention for article published in Molecular Psychiatry, March 2017
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About this Attention Score

  • In the top 5% of all research outputs scored by Altmetric
  • High Attention Score compared to outputs of the same age (97th percentile)
  • High Attention Score compared to outputs of the same age and source (96th percentile)

Citations

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Title
Identification of a novel, fast-acting GABAergic antidepressant
Published in
Molecular Psychiatry, March 2017
DOI 10.1038/mp.2017.14
Pubmed ID
Authors

K M J McMurray, M J Ramaker, A M Barkley-Levenson, P S Sidhu, P K Elkin, M K Reddy, M L Guthrie, J M Cook, V H Rawal, L A Arnold, S C Dulawa, A A Palmer

Abstract

Current pharmacotherapies for depression exhibit slow onset, side effects and limited efficacy. Therefore, identification of novel fast-onset antidepressants is desirable. GLO1 is a ubiquitous cellular enzyme responsible for the detoxification of the glycolytic byproduct methylglyoxal (MG). We have previously shown that MG is a competitive partial agonist at GABA-A receptors. We examined the effects of genetic and pharmacological inhibition of GLO1 in two antidepressant assay models: the tail suspension test (TST) and the forced swim test (FST). We also examined the effects of GLO1 inhibition in three models of antidepressant onset: the chronic FST (cFST), chronic mild stress (CMS) paradigm and olfactory bulbectomy (OBX). Genetic knockdown of Glo1 or pharmacological inhibition using two structurally distinct GLO1 inhibitors (S-bromobenzylglutathione cyclopentyl diester (pBBG) or methyl-gerfelin (MeGFN)) reduced immobility in the TST and acute FST. Both GLO1 inhibitors also reduced immobility in the cFST after 5 days of treatment. In contrast, the serotonin reuptake inhibitor fluoxetine (FLX) reduced immobility after 14, but not 5 days of treatment. Furthermore, 5 days of treatment with either GLO1 inhibitor blocked the depression-like effects induced by CMS on the FST and coat state, and attenuated OBX-induced locomotor hyperactivity. Finally, 5 days of treatment with a GLO1 inhibitor (pBBG), but not FLX, induced molecular markers of the antidepressant response including brain-derived neurotrophic factor (BDNF) induction and increased phosphorylated cyclic-AMP response-binding protein (pCREB) to CREB ratio in the hippocampus and medial prefrontal cortex (mPFC). Our findings indicate that GLO1 inhibitors may provide a novel and fast-acting pharmacotherapy for depression.Molecular Psychiatry advance online publication, 21 March 2017; doi:10.1038/mp.2017.14.

Twitter Demographics

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Mendeley readers

The data shown below were compiled from readership statistics for 60 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Austria 1 2%
Unknown 59 98%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 14 23%
Researcher 10 17%
Student > Master 9 15%
Student > Bachelor 9 15%
Student > Postgraduate 4 7%
Other 9 15%
Unknown 5 8%
Readers by discipline Count As %
Neuroscience 17 28%
Medicine and Dentistry 7 12%
Agricultural and Biological Sciences 7 12%
Biochemistry, Genetics and Molecular Biology 4 7%
Nursing and Health Professions 3 5%
Other 9 15%
Unknown 13 22%

Attention Score in Context

This research output has an Altmetric Attention Score of 124. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 07 October 2020.
All research outputs
#189,597
of 17,371,891 outputs
Outputs from Molecular Psychiatry
#164
of 3,250 outputs
Outputs of similar age
#6,030
of 273,390 outputs
Outputs of similar age from Molecular Psychiatry
#3
of 55 outputs
Altmetric has tracked 17,371,891 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 98th percentile: it's in the top 5% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 3,250 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 29.4. This one has done particularly well, scoring higher than 94% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 273,390 tracked outputs that were published within six weeks on either side of this one in any source. This one has done particularly well, scoring higher than 97% of its contemporaries.
We're also able to compare this research output to 55 others from the same source and published within six weeks on either side of this one. This one has done particularly well, scoring higher than 96% of its contemporaries.