The central theme of the lab is adult hippocampal neurogenesis, which is implicated in memory formation and mood regulation. We investigate environmental and molecular mechanisms controlling the production of these adult-born neurons and how they impact mental health. We study neurogenesis in healthy ageing as well as in the context of diseases such as Alzheimer’s and depression. By approaching neurogenesis in health and disease, the strategy is two folds:

Validating the neurogenic process as a target for prevention and pharmacological interventions.
Developing neurogenesis as a biomarker of disease prediction and progression.

The Adult Neurogenesis & Mental Health Laboratory

Ongoing projects in the Thuret Lab

Mechanisms underlying the role of gut-microbiota in exercise-induced changes in cognitive function in middle-age

This project will decipher the dialogue between the brain, the gut microbiota and exercise by investigating the impact of a 12-week online exercise intervention in healthy middle-aged community-dwelling adults who do not habitually exercise on global cognition, hippocampus-dependent cognition, mood, quality of life and brain-derived neurotrophic factor. Serum samples will be used in our in vitro parabiosis assay to gain insights into the corresponding impact on the neurogenic process. Whilst stool samples will be collected for our collaborators at University College Cork to elucidate the impact on the gut microbiota and metabolomic profile. This project is led by postdoc Dr Curie Kim.

Ongoing projects in the Thuret Lab

Developing and validating a biomarker assay using neural stem cells in vitro to predict and follow Alzheimer’s disease progression

Adult hippocampal neurogenesis is important for learning and memory and is altered early in Alzheimer’s disease. We developed a unique assay to model the impact of the systemic environment on hippocampal neurogenesis in vitro, and subsequently used it to analyse serum samples of individuals with mild cognitive impairment (MCI) to predict progression to clinical Alzheimer's disease. A subset of ‘baseline’ cellular readouts together with education level were able to predict MCI to Alzheimer's disease progression with high sensitivity and specificity. The aim of the current project is to validate the in vitro neurogenesis assay in larger, independent cohorts, to investigate the robustness and precision of the assay and to increase throughput using automation. The in vitro neurogenesis assay will also be used to explore the molecular and cellular mechanisms in Alzheimer's disease pathogenesis.

Ongoing projects in the Thuret Lab

Investigating the impact of exercise on neural stem cells and cognition: uncovering molecular mechanisms and exercise mimetic drugs.

This project focuses on identifying the molecular mechanisms by which exercise modulates adult hippocampal neurogenesis (AHN), and cognition in addition to uncovering anti-ageing/cognition-enhancing exercise mimetic drugs. In order to do this, the samples from the responders (a group of participants who showed improvement in pattern separation task following a 12 week exercise trial) will be investigated using a wide range of techniques. Later, connectivity mapping will be used for discovery and validation of exercise mimetic drugs. This project is led by PhD student Sahand Farmand.

Ongoing projects in the Thuret Lab

ACID: a randomised controlled clinical trial investigating the role of purified anthocyanins in older adults at risk for dementia

Anthocyanins are dietary flavonoids with strong anti-oxidant capacities, mostly found in dark berries and fruits. ACID is a 24-week intervention during which older individuals (60+) at risk for dementia are given capsules containing purified anthocyanins or placebos. The main study aim is to assess the potential of these supplements in delaying cognitive decline. Thoroughout the trial we have collected a wide range of biomarkers to establish how anthocyanins infer their protective effects. Most notably, longitudinal cerebrospinal fluid and blood sample collection allowed for repeat measurements of circulating ACN metabolites. Alongside this, analyses aimed at delineating the trial’s effects on neuroimaging paramerers, the gut microbiome, blood and CSF inflammation and blood lipid and metabolite profiles are also currently ongoing. Blood-derived serum was also collected at baseline and endpoint and is being used to carry out the Thuret lab’s in vitro parabiosis assay. This will help us establish wether anthocyanin suplementatio alters the neurogenic process. This project is led by postdoctoral research fellow Dr. de Lucia who is funded by a Helse Vest fellowship.

The impact of Psilocybin on Mood and Cognitive Function mediated by Hippocampal Neurogenesis and Microglia in patients with Major Depressive Disorder

This project will investigate the impact of psilocybin, a psychedelic compound capable of alleviating symptoms of depression, on adult hippocampal neurogenesis and microglial polarisation. Human cellular models involving hippocampal and microglial stem cell lines will be used to determine mechanisms underlying mood and cognitive function changes in depressed patients. An ongoing RCT led by Dr James Rucker and Prof. Allan Young, will assess the efficacy of psilocybin-assisted therapy for treatment-resistant major depressive disorder (PsiDeR). Serum from trial participants will be applied to the in vitro parabiosis assay developed by the Thuret Lab to establish changes in neurogenic markers, as a proxy biomarker for neurogenesis. This project is led by PhD-student Zarah Haniff.