PMID- 37118117
OWN - NLM
STAT- MEDLINE
DCOM- 20230501
LR  - 20240202
IS  - 2662-8465 (Electronic)
IS  - 2662-8465 (Linking)
VI  - 3
IP  - 2
DP  - 2023 Feb
TI  - Systemic GDF11 attenuates depression-like phenotype in aged mice via stimulation 
      of neuronal autophagy.
PG  - 213-228
LID - 10.1038/s43587-022-00352-3 [doi]
AB  - Cognitive decline and mood disorders increase in frequency with age. Many efforts 
      are focused on the identification of molecules and pathways to treat these 
      conditions. Here, we demonstrate that systemic administration of growth 
      differentiation factor 11 (GDF11) in aged mice improves memory and alleviates 
      senescence and depression-like symptoms in a neurogenesis-independent manner. 
      Mechanistically, GDF11 acts directly on hippocampal neurons to enhance neuronal 
      activity via stimulation of autophagy. Transcriptomic and biochemical analyses of 
      these neurons reveal that GDF11 reduces the activity of mammalian target of 
      rapamycin (mTOR), a master regulator of autophagy. Using a murine model of 
      corticosterone-induced depression-like phenotype, we also show that GDF11 
      attenuates the depressive-like behavior of young mice. Analysis of sera from 
      young adults with major depressive disorder (MDD) reveals reduced GDF11 levels. 
      These findings identify mechanistic pathways related to GDF11 action in the brain 
      and uncover an unknown role for GDF11 as an antidepressant candidate and 
      biomarker.
CI  - (c) 2023. The Author(s).
FAU - Moigneu, Carine
AU  - Moigneu C
AD  - Perception and Memory Lab, Institut Pasteur, Universite Paris Cite, CNRS UMR3571, 
      Paris, France.
FAU - Abdellaoui, Soumia
AU  - Abdellaoui S
AD  - Perception and Memory Lab, Institut Pasteur, Universite Paris Cite, CNRS UMR3571, 
      Paris, France.
AD  - Institut Necker Enfants Malades, INSERM UMR-S1151, Universite Paris Cite, Paris, 
      France.
FAU - Ramos-Brossier, Mariana
AU  - Ramos-Brossier M
AUID- ORCID: 0000-0003-3099-4192
AD  - Institut Necker Enfants Malades, INSERM UMR-S1151, Universite Paris Cite, Paris, 
      France.
FAU - Pfaffenseller, Bianca
AU  - Pfaffenseller B
AD  - Department of Psychiatry and Behavioural Neurosciences, McMaster University, 
      Hamilton, ON, Canada.
FAU - Wollenhaupt-Aguiar, Bianca
AU  - Wollenhaupt-Aguiar B
AD  - Department of Psychiatry and Behavioural Neurosciences, McMaster University, 
      Hamilton, ON, Canada.
FAU - de Azevedo Cardoso, Taiane
AU  - de Azevedo Cardoso T
AD  - Department of Psychiatry and Behavioural Neurosciences, McMaster University, 
      Hamilton, ON, Canada.
FAU - Camus, Claire
AU  - Camus C
AD  - Perception and Memory Lab, Institut Pasteur, Universite Paris Cite, CNRS UMR3571, 
      Paris, France.
FAU - Chiche, Aurelie
AU  - Chiche A
AD  - Cellular Plasticity in Age-Related Pathologies Laboratory, Institut Pasteur, 
      Universite Paris Cite, CNRS UMR3738, Paris, France.
FAU - Kuperwasser, Nicolas
AU  - Kuperwasser N
AD  - Institut Necker Enfants Malades, INSERM UMR-S1151, Universite Paris Cite, Paris, 
      France.
FAU - Azevedo da Silva, Ricardo
AU  - Azevedo da Silva R
AD  - Department of Health and Behavior, Catholic University of Pelotas, Pelotas, 
      Brazil.
FAU - Pedrotti Moreira, Fernanda
AU  - Pedrotti Moreira F
AUID- ORCID: 0000-0002-3672-7231
AD  - Department of Health and Behavior, Catholic University of Pelotas, Pelotas, 
      Brazil.
FAU - Li, Han
AU  - Li H
AD  - Cellular Plasticity in Age-Related Pathologies Laboratory, Institut Pasteur, 
      Universite Paris Cite, CNRS UMR3738, Paris, France.
FAU - Oury, Franck
AU  - Oury F
AUID- ORCID: 0000-0003-0562-9900
AD  - Institut Necker Enfants Malades, INSERM UMR-S1151, Universite Paris Cite, Paris, 
      France.
FAU - Kapczinski, Flavio
AU  - Kapczinski F
AD  - Department of Psychiatry and Behavioural Neurosciences, McMaster University, 
      Hamilton, ON, Canada.
AD  - Instituto Nacional de Ciencia e Tecnologia Translacional em Medicina (INCT-TM), 
      Porto Alegre, Brazil.
AD  - Department of Psychiatry, Universidade Federal do Rio Grande do Sul (UFRGS), 
      Porto Alegre, Brazil.
FAU - Lledo, Pierre-Marie
AU  - Lledo PM
AUID- ORCID: 0000-0002-8156-7003
AD  - Perception and Memory Lab, Institut Pasteur, Universite Paris Cite, CNRS UMR3571, 
      Paris, France. pmlledo@pasteur.fr.
FAU - Katsimpardi, Lida
AU  - Katsimpardi L
AUID- ORCID: 0000-0001-5688-7104
AD  - Perception and Memory Lab, Institut Pasteur, Universite Paris Cite, CNRS UMR3571, 
      Paris, France. lida.katsimpardi@inserm.fr.
AD  - Institut Necker Enfants Malades, INSERM UMR-S1151, Universite Paris Cite, Paris, 
      France. lida.katsimpardi@inserm.fr.
LA  - eng
GR  - R01 DC015137/DC/NIDCD NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20230202
PL  - United States
TA  - Nat Aging
JT  - Nature aging
JID - 101773306
RN  - 0 (Growth Differentiation Factors)
RN  - 0 (Gdf11 protein, mouse)
RN  - 0 (Bone Morphogenetic Proteins)
SB  - IM
CIN - Nat Aging. 2023 Feb;3(2):148-150. PMID: 37118123
EIN - Nat Aging. 2023 Aug;3(8):1036. PMID: 37328576
MH  - Mice
MH  - Animals
MH  - *Depression/drug therapy
MH  - *Depressive Disorder, Major/drug therapy
MH  - Growth Differentiation Factors/genetics
MH  - Phenotype
MH  - Autophagy/genetics
MH  - Mammals/metabolism
MH  - Bone Morphogenetic Proteins/genetics
PMC - PMC10154197
COIS- The authors declare no competing interests.
EDAT- 2023/04/29 06:04
MHDA- 2023/05/01 06:42
PMCR- 2023/02/02
CRDT- 2023/04/28 23:36
PHST- 2021/02/05 00:00 [received]
PHST- 2022/12/19 00:00 [accepted]
PHST- 2023/05/01 06:42 [medline]
PHST- 2023/04/29 06:04 [pubmed]
PHST- 2023/04/28 23:36 [entrez]
PHST- 2023/02/02 00:00 [pmc-release]
AID - 10.1038/s43587-022-00352-3 [pii]
AID - 352 [pii]
AID - 10.1038/s43587-022-00352-3 [doi]
PST - ppublish
SO  - Nat Aging. 2023 Feb;3(2):213-228. doi: 10.1038/s43587-022-00352-3. Epub 2023 Feb 
      2.