Summary: In adults, levels of GDF11, a key gene for murine neural stem cell regeneration, are inversely related to depressive episodes. Administration of GDF11 proteins to aging mice reduced depression and improved cognition.
Source: Pastor Institute
The aging process is often linked to the onset of cognitive decline, depression and memory loss. Scientists from the Institut Pasteur, CNRS and Inserm have discovered that the administration of the GDF11 protein, known to regenerate murine neural stem cells, improves cognitive abilities and reduces depression in elderly mice.
They also demonstrated the mechanism of action of this protein in different mouse models. The scientists then further explored these findings in relation to depression and showed that in humans, GDF11 levels are inversely related to depressive episodes.
The results of this study have been published in the journal natural aging on February 2, 2023.
The aging process is often linked to the onset of neurological symptoms such as cognitive decline, memory loss or mood disorders such as depression. Previous studies have shown that the growth factor GDF11, a protein present in the blood, has a beneficial effect on olfactory perception and on the generation of new cells in the brains of aged mice. The mechanism of action of GDF11 in the brain has remained unknown.
Researchers from the Institut Pasteur, CNRS and Inserm have discovered that long-term administration of the GDF11 protein to elderly mice improves their memory and significantly reduces behavioral disorders linked to depression, allowing them to find a behavior similar to that observed in younger mice.
The scientists carried out other studies on different models of aged mice or on models of mice with behavioral disorders such as depression and in vitro neuronal cultures, which enabled them to identify the molecular mechanism of action of GDF11.
They discovered that the administration of GDF11 activates the natural process of intracellular cleaning, called “autophagy”, in the brain and the elimination of senescent cells. The GDF11 protein thus indirectly increases cell renewal in the hippocampus and restores neuronal activity.
To better understand the link between depressive disorders and the GDF11 protein in humans, scientists from the Institut Pasteur, CNRS and Inserm, in collaboration with scientists from McMaster University, quantified the protein in blood serum from an international cohort of young patients with major depression. mess.
They observed that GDF11 levels are significantly lower in these patients. Moreover, by measuring the levels of this protein at different stages, the scientists observed a fluctuation of the level depending on the depressive state.
“This work provides clinical evidence linking low blood levels of GDF11 to mood disorders in patients with depression,” said Lida Katsimpardi, researcher in the Perception and Memory Unit at the Institut Pasteur, affiliated with the ‘Inserm at the Institut Necker-Enfants Malades, and co-last author of the study.
“In the future, this molecule could be used as a biomarker to diagnose depressive episodes. It could also serve as a therapeutic molecule for the treatment of cognitive and affective disorders,” she concludes.
About this depression and genetic research news
Author: Anne Burlet-Parendel
Source: Pastor Institute
Contact: Anne Burlet-Parendel – Pasteur Institute
Picture: The image is credited to the Perception and Memory Unit – Institut Pasteur
Original research: Free access.
“Systemic GDF11 attenuates depression-like phenotype in aged mice via stimulation of neuronal autophagy” by Carine Moigneu et al. natural aging
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Abstract
Systemic GDF11 attenuates depression-like phenotype in aged mice via stimulation of neuronal autophagy
Cognitive decline and mood disorders increase in frequency with age. Many efforts are focused on identifying 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 symptoms of senescence and depression in a neurogenesis-independent manner.
Mechanically, GDF11 acts directly on hippocampal neurons to enhance neuronal activity via stimulation of autophagy. Transcriptomic and biochemical analyzes of these neurons reveal that GDF11 reduces the activity of the mammalian target of rapamycin (mTOR), a master regulator of autophagy.
Using a mouse model of corticosterone-induced depression-like phenotype, we also show that GDF11 attenuates depression-like behavior in young mice. Analysis of sera from young adults with major depressive disorder (MDD) reveals reduced levels of GDF11.
These results identify mechanistic pathways related to GDF11 action in the brain and reveal an unknown role of GDF11 as an antidepressant candidate and biomarker.