King's College London

Published in Molecular Psychiatry, the researchers developed an assay, an experimental method, to observe how new neurons respond to a late-life depression-like environment. They found that late-life depression was associated with changes in neurogenesis - the process by which new neurons are formed - and discovered that diet may be driving these changes.

Late-life depression affects the physical, emotional, and social wellbeing of individuals. It is frequently observed together with cognitive decline and/or dementia, so treating one could improve the symptoms of the others. While pharmacological treatments are available for depression, researchers are now exploring environment and lifestyle modifications for prevention and treatment.

In this study, researchers from the Thuret Group looked at neurogenesis in the hippocampus - a part of the brain primarily associated with learning and memory and the shrinkage of which has been associated with depression. Neurogenesis encompasses the stages of cells' birth, proliferation (cell growth and division), differentiation (stem cell undergoing a complex process to become a more specific type of cell), and cell death (this can occur at any stage as a method to control cell numbers).

As it is currently impossible to observe neurogenesis in live humans, the researchers developed an assay where they incubate hippocampal stem cells with blood samples, allowing cells to receive signals from the blood. It has been demonstrated that this assay mimics a circulatory living system, where the brain receives signals from the rest of the body via the blood.

In this study, the blood samples used were collected at the start of an epidemiology study from participants of the Three-City study cohort in Bordeaux, France, who were followed over a 12-year period. Comparing the cells treated with these samples allowed the researchers to follow the progression of the same individuals, some of whom developed depression.

The researchers found that when late-life depression developed in the participants, the numbers of cells undergoing proliferation and differentiation changed. They also saw abnormal cell morphology (cell shape and arrangement, which affects neuron function) in participants with recurring depression. This abnormality was not seen in participants with a single occurrence of depression, suggesting that while late-life depression can affect neurogenesis, it is multiple incidents of depression that cause lasting effects in neuron function.

The researchers also demonstrated that changes in dietary factors may be driving these neurogenesis-associated changes specifically in those with late-life depression. In this study, they identified two factors: glycerophospholipid, a fat substance, and butyrylcarnitine, a substance produced when the body breaks down food for energy. Both substances are metabolites, products of human metabolism.

The exact biological mechanism underlying the relationship between these factors is still unknown. Dr Andrea Du Preez, the first author of this study, commented "The next step is to fully understand how the metabolites and lipids we identified can modulate hippocampal neurogenesis in the context of depression"

The neurogenesis assay developed by the Thuret Group has also been used to study other memory and learning-affected conditions such as Alzheimer’s, cognitive decline, and dementia.

This study was part of the EU consortium DCogPlast “Diet Cognition and Plasticity” funded by JPI-HDHL and the BMWFW. Impaired hippocampal neurogenesis in vitro is modulated by dietary-related endogenous factors and associated with depression in a longitudinal ageing cohort study (DOI: 10.1038/s41380-022-01644-1) was published in Molecular Psychiatry.

For more information, please contact Annora Thoeng (School of Neuroscience Senior Communications and Engagement Officer)