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 1,229 tweeters who shared this research output. Click here to find out more about how the information was compiled.

Geographical breakdown

Country	Count	As %
Japan	331	27%
United States	76	6%
United Kingdom	22	2%
Canada	12	<1%
Spain	10	<1%
Australia	5	<1%
Mexico	4	<1%
Sweden	4	<1%
France	4	<1%
Other	70	6%
Unknown	691	56%

Demographic breakdown

Type	Count	As %
Members of the public	1130	92%
Scientists	52	4%
Practitioners (doctors, other healthcare professionals)	36	3%
Science communicators (journalists, bloggers, editors)	9	<1%
Unknown	2	<1%

Mendeley readers

The data shown below were compiled from readership statistics for 773 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country	Count	As %
United States	8	1%
Japan	4	<1%
United Kingdom	4	<1%
Germany	3	<1%
Canada	3	<1%
Switzerland	2	<1%
Spain	2	<1%
Ireland	1	<1%
France	1	<1%
Other	7	<1%
Unknown	738	95%

Demographic breakdown

Readers by professional status	Count	As %
Student > Ph. D. Student	136	18%
Researcher	129	17%
Student > Bachelor	114	15%
Student > Master	98	13%
Student > Doctoral Student	48	6%
Other	134	17%
Unknown	114	15%

Readers by discipline	Count	As %
Agricultural and Biological Sciences	170	22%
Medicine and Dentistry	115	15%
Biochemistry, Genetics and Molecular Biology	108	14%
Neuroscience	76	10%
Psychology	42	5%
Other	111	14%
Unknown	151	20%

Attention Score in Context

This research output has an Altmetric Attention Score of 785. 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 01 April 2022.

All research outputs

#17,178

of 21,255,122 outputs

Outputs from Cell

#146

of 16,270 outputs

Outputs of similar age

#116

of 225,076 outputs

Outputs of similar age from Cell

of 144 outputs

Altmetric has tracked 21,255,122 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 16,270 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 49.7. 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 225,076 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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