TY - JOUR
T1 - Impaired hippocampal neurogenesis in vitro is modulated by dietary-related endogenous factors and associated with depression in a longitudinal ageing cohort study
AU - Du Preez, Andrea
AU - Lefèvre-Arbogast, Sophie
AU - González-Domínguez, Raúl
AU - Houghton, Vikki
AU - de Lucia, Chiara
AU - Low, Dorrain Y.
AU - Helmer, Catherine
AU - Féart, Catherine
AU - Delcourt, Cécile
AU - Proust-Lima, Cécile
AU - Pallàs, Mercè
AU - Sánchez-Pla, Alex
AU - Urpi-Sardà, Mireia
AU - Ruigrok, Silvie R.
AU - Altendorfer, Barbara
AU - Aigner, Ludwig
AU - Lucassen, Paul J.
AU - Korosi, Aniko
AU - Manach, Claudine
AU - Andres-Lacueva, Cristina
AU - Samieri, Cécilia
AU - Thuret, Sandrine
N1 - Funding Information:
PJL and AK are supported by Alzheimer Nederland and the NWO Food & Cognition program, PJL is supported by the Urban Mental Health program of the University of Amsterdam. SLA was part of the University Research school (Ecole Universitaire de Recherche, EUR) Digital Public Health PhD program, supported within the framework of the French National Research Agency (ANR) “Programme d’Investissement d’Avenir” (Investment for the Future) PIA3 (17-EURE-0019). The Three-City Study was conducted under a partnership agreement between the Institut National de la Santé et de la Recherche Médicale (INSERM), the Institut de Santé Publique et Développement of the Victor Segalen Bordeaux 2 University and Sanofi-Aventis. The Fondation pour la Recherche Médicale funded the preparation and initiation of the study. The 3C Study was also supported by the Caisse Nationale Maladie des Travailleurs Salariés, Direction Générale de la Santé, Mutuelle Générale de l’Education Nationale, Institut de la Longévité, Regional Governments of Aquitaine and Bourgogne, Fondation de France, Ministry of Research-INSERM Programme “Cohortes et collections de données biologiques”, French National Research Agency COGINUT ANR-06-PNRA-005, the Fondation Plan Alzheimer (FCS 2009–2012), and the Caisse Nationale pour la Solidarité et l’Autonomie (CNSA).
Funding Information:
This project was part of the EU consortium DCogPlast “Diet Cognition and Plasticity” funded by JPI-HDHL (Medical Research Council UK: MR/N030087/1; French National Research Agency ANR-15-HDHL-0002-05; PCIN-2015-229- MINECO; CiberFES- Cofund by FEDER Program from EU, 2017SGR1546 & ICREA 2018 Academia Award from the Generalitat de Catalunya), the BMWFW under BMWFW-10.420/0009-WF/V/3c/2015.
Publisher Copyright:
© 2022, The Author(s).
PY - 2022/8
Y1 - 2022/8
N2 - Environmental factors like diet have been linked to depression and/or relapse risk in later life. This could be partially driven by the food metabolome, which communicates with the brain via the circulatory system and interacts with hippocampal neurogenesis (HN), a form of brain plasticity implicated in depression aetiology. Despite the associations between HN, diet and depression, human data further substantiating this hypothesis are largely missing. Here, we used an in vitro model of HN to test the effects of serum samples from a longitudinal ageing cohort of 373 participants, with or without depressive symptomology. 1% participant serum was applied to human fetal hippocampal progenitor cells, and changes in HN markers were related to the occurrence of depressive symptoms across a 12-year period. Key nutritional, metabolomic and lipidomic biomarkers (extracted from participant plasma and serum) were subsequently tested for their ability to modulate HN. In our assay, we found that reduced cell death and increased neuronal differentiation were associated with later life depressive symptomatology. Additionally, we found impairments in neuronal cell morphology in cells treated with serum from participants experiencing recurrent depressive symptoms across the 12-year period. Interestingly, we found that increased neuronal differentiation was modulated by increased serum levels of metabolite butyrylcarnitine and decreased glycerophospholipid, PC35:1(16:0/19:1), levels – both of which are closely linked to diet – all in the context of depressive symptomology. These findings potentially suggest that diet and altered HN could subsequently shape the trajectory of late-life depressive symptomology.
AB - Environmental factors like diet have been linked to depression and/or relapse risk in later life. This could be partially driven by the food metabolome, which communicates with the brain via the circulatory system and interacts with hippocampal neurogenesis (HN), a form of brain plasticity implicated in depression aetiology. Despite the associations between HN, diet and depression, human data further substantiating this hypothesis are largely missing. Here, we used an in vitro model of HN to test the effects of serum samples from a longitudinal ageing cohort of 373 participants, with or without depressive symptomology. 1% participant serum was applied to human fetal hippocampal progenitor cells, and changes in HN markers were related to the occurrence of depressive symptoms across a 12-year period. Key nutritional, metabolomic and lipidomic biomarkers (extracted from participant plasma and serum) were subsequently tested for their ability to modulate HN. In our assay, we found that reduced cell death and increased neuronal differentiation were associated with later life depressive symptomatology. Additionally, we found impairments in neuronal cell morphology in cells treated with serum from participants experiencing recurrent depressive symptoms across the 12-year period. Interestingly, we found that increased neuronal differentiation was modulated by increased serum levels of metabolite butyrylcarnitine and decreased glycerophospholipid, PC35:1(16:0/19:1), levels – both of which are closely linked to diet – all in the context of depressive symptomology. These findings potentially suggest that diet and altered HN could subsequently shape the trajectory of late-life depressive symptomology.
UR - http://www.scopus.com/inward/record.url?scp=85133588029&partnerID=8YFLogxK
U2 - 10.1038/s41380-022-01644-1
DO - 10.1038/s41380-022-01644-1
M3 - Article
AN - SCOPUS:85133588029
SN - 1359-4184
VL - 27
SP - 3425
EP - 3440
JO - Molecular Psychiatry
JF - Molecular Psychiatry
IS - 8
ER -