Report for: Skeletal Muscle PGC-1α1 Modulates Kynurenine Metabolism and Mediates Resilience to Stress-Induced Depression

Title	Skeletal Muscle PGC-1α1 Modulates Kynurenine Metabolism and Mediates Resilience to Stress-Induced Depression
Published in	Cell, September 2014
DOI	10.1016/j.cell.2014.07.051
Pubmed ID	25259918
Authors	Leandro Z. Agudelo, Teresa Femenía, Funda Orhan, Margareta Porsmyr-Palmertz, Michel Goiny, Vicente Martinez-Redondo, Jorge C. Correia, Manizheh Izadi, Maria Bhat, Ina Schuppe-Koistinen, Amanda T. Pettersson, Duarte M.S. Ferreira, Anna Krook, Romain Barres, Juleen R. Zierath, Sophie Erhardt, Maria Lindskog, Jorge L. Ruas
Abstract	Depression is a debilitating condition with a profound impact on quality of life for millions of people worldwide. Physical exercise is used as a treatment strategy for many patients, but the mechanisms that underlie its beneficial effects remain unknown. Here, we describe a mechanism by which skeletal muscle PGC-1α1 induced by exercise training changes kynurenine metabolism and protects from stress-induced depression. Activation of the PGC-1α1-PPARα/δ pathway increases skeletal muscle expression of kynurenine aminotransferases, thus enhancing the conversion of kynurenine into kynurenic acid, a metabolite unable to cross the blood-brain barrier. Reducing plasma kynurenine protects the brain from stress-induced changes associated with depression and renders skeletal muscle-specific PGC-1α1 transgenic mice resistant to depression induced by chronic mild stress or direct kynurenine administration. This study opens therapeutic avenues for the treatment of depression by targeting the PGC-1α1-PPAR axis in skeletal muscle, without the need to cross the blood-brain barrier.

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Twitter Demographics

The data shown below were collected from the profiles of 1,292 tweeters who shared this research output. Click here to find out more about how the information was compiled.

Geographical breakdown

Country	Count	As %
Japan	346	27%
United States	79	6%
United Kingdom	26	2%
Spain	14	1%
Canada	14	1%
China	7	<1%
Korea, Republic of	5	<1%
Australia	5	<1%
Germany	4	<1%
Other	64	5%
Unknown	728	56%

Demographic breakdown

Type	Count	As %
Members of the public	1192	92%
Scientists	52	4%
Practitioners (doctors, other healthcare professionals)	35	3%
Science communicators (journalists, bloggers, editors)	11	<1%
Unknown	2	<1%

Mendeley readers

The data shown below were compiled from readership statistics for 563 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country	Count	As %
United States	7	1%
Japan	4	<1%
United Kingdom	4	<1%
Sweden	3	<1%
Germany	3	<1%
France	3	<1%
Canada	3	<1%
Spain	2	<1%
Switzerland	2	<1%
Other	10	2%
Unknown	522	93%

Demographic breakdown

Readers by professional status	Count	As %
Student > Ph. D. Student	106	19%
Researcher	105	19%
Student > Bachelor	91	16%
Student > Master	76	13%
Unspecified	42	7%
Other	143	25%

Readers by discipline	Count	As %
Agricultural and Biological Sciences	163	29%
Medicine and Dentistry	101	18%
Biochemistry, Genetics and Molecular Biology	75	13%
Unspecified	66	12%
Neuroscience	52	9%
Other	106	19%

Attention Score in Context

This research output has an Altmetric Attention Score of 777. 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 16 October 2019.

All research outputs

#6,970

of 13,644,932 outputs

Outputs from Cell

#55

of 14,758 outputs

Outputs of similar age

#90

of 210,453 outputs

Outputs of similar age from Cell

of 144 outputs

Altmetric has tracked 13,644,932 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 99th percentile: it's in the top 5% of all research outputs ever tracked by Altmetric.

So far Altmetric has tracked 14,758 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 30.1. This one has done particularly well, scoring higher than 99% 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 210,453 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 99% of its contemporaries.

We're also able to compare this research output to 144 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 98% of its contemporaries.

Skeletal Muscle PGC-1α1 Modulates Kynurenine Metabolism and Mediates Resilience to Stress-Induced Depression

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