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 1,276 tweeters who shared this research output. Click here to find out more about how the information was compiled.

Geographical breakdown

Country	Count	As %
Japan	348	27%
United States	76	6%
United Kingdom	23	2%
Canada	13	1%
Spain	13	1%
China	5	<1%
Germany	5	<1%
Australia	5	<1%
Mexico	4	<1%
Other	61	5%
Unknown	723	57%

Demographic breakdown

Type	Count	As %
Members of the public	1174	92%
Scientists	54	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 621 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country	Count	As %
United States	8	1%
United Kingdom	4	<1%
Japan	4	<1%
France	3	<1%
Canada	3	<1%
Germany	3	<1%
Switzerland	2	<1%
Spain	2	<1%
Sweden	2	<1%
Other	9	1%
Unknown	581	94%

Demographic breakdown

Readers by professional status	Count	As %
Student > Ph. D. Student	117	19%
Researcher	116	19%
Student > Bachelor	92	15%
Student > Master	78	13%
Student > Doctoral Student	38	6%
Other	124	20%
Unknown	56	9%

Readers by discipline	Count	As %
Agricultural and Biological Sciences	163	26%
Medicine and Dentistry	107	17%
Biochemistry, Genetics and Molecular Biology	82	13%
Neuroscience	60	10%
Psychology	41	7%
Other	88	14%
Unknown	80	13%

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 12 April 2020.

All research outputs

#8,994

of 15,138,549 outputs

Outputs from Cell

#67

of 15,054 outputs

Outputs of similar age

#96

of 210,711 outputs

Outputs of similar age from Cell

of 144 outputs

Altmetric has tracked 15,138,549 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 15,054 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 33.9. 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 210,711 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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