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Home | Institute of Psychiatry, Psychology & Neuroscience | Basic & Clinical Neuroscience | Our
research | Cells & behaviour | Adult Neurogenesis & Mental Health | About us
ADULT NEUROGENESIS & MENTAL HEALTH
About us

Dr Sandrine Thuret , PhD

Thuret

Principal Investigator & Lecturer in Neural Stem Cell Research

Figure 1 Theme

The central theme of the lab is postnatal or adult hippocampal neurogenesis (AHN), which is
implicated in memory formation and mood regulation. We investigate environmental and
molecular regulatory mechanisms controlling AHN by using in vitro approaches (human
hippocampal stem cells) for molecular focused studies and mice as animal models for
behavioural centred investigations.
We study AHN (i) in a healthy context- such as the effect of diet or the changes occurring upon
healthy ageing but also (ii) in the context of diseases such as Alzheimers disease and
depression. By approaching AHN in the context of health & disease, the strategy is two folds: (i)
validating AHN as a target for prevention and pharmacological interventions as well as (ii)
developing AHN as a biomarker of disease prediction and progression.
Lab Description

The adult mammalian brain contains small populations of neural stem cells dividing and
differentiating into neurons. This process of neurogenesis occurs in the subgranular zone of the
hippocampal dentate gyrus. AHN decreases with age and elderly animals display impaired
learning and memory abilities, whereas increased AHN is linked to improved learning and
memory. Moreover, AHN is reduced by stressful experiences and in animal models of
depression, whereas many antidepressant treatments have been shown to enhance and are
dependent on functional AHN. Therefore, AHN strongly emerges as an advantageous target for
counteracting the effect of ageing and stress and thus preventing cognitive and mood decline.
In the Thuret lab we investigate the molecular mechanisms governing neurogenesis by using
human hippocampal cell lines and we use the mouse as animal model to study cognition and
mood. We perform a wide range of molecular biology and histology techniques with both in vivo
and in vitro models. We are currently studying the molecular mechanisms by which
environment (i.e. diet) and diseases (i.e. Alzheimers Disease) impacts on AHN and subsequently
affect cognition and mood.

Research Projects

Alzheimers Disease and Healthy Ageing

We study how the systemic milieu modulates hippocampal neurogenesis during ageing and
Alzheimers disease progression.
Depression
We have developed an in vitro model of stress using human hippocampal progenitor cells. We
use this model to study the preventive and treatment mode of action of compounds on
decreased neurogenesis induced by stress. We are studying the role of the systemic milieu,
inflammation and stress in mediating the changes in neurogenesis in depression.
Nutrition
We study the molecular mechanisms (including epigenetic changes and modification in
microRNA expression) by which diet content and meal frequency impacts on adult hippocampal
neurogenesis and subsequently affects cognition and mood.
We are also investigating if certain bioactives previously shown to have beneficial effect on
cognition and mood can regulate adult hippocampal neurogenesis. Furthermore we are studying
if their effect on cognition and mood is mediated by changes in neurogenesis.
physiological and environmental modulation of Adult Hippocampal Neurogenesis

Fig.1: Schematic representation of the sagittal view of a rodent brain highlighting the two
neurogenic zones of the adult mammalian brain: The subventricular zone (SVZ) of the lateral
ventricles and the subgranular zone of the dentate gyrus (DG) in the hippocampus. Neurons
generated in the SVZ migrate through the rostral migratory stream (RMS) and are incorporated
into the olfactory bulb. The hippocampal region contained in the black square is enlarged
showing (1) neural progenitor cells in the in the subgranular zone of the dentate gyrus
proliferating, (2) migrating into the granule cell layer and (3) maturing into new granule
neurons, integrating into the hippocampal circuitry by receiving inputs from the entorhinal
cortex, and extend projections into the CA3 (Stangl & Thuret, 2009).

Schematic representation of the sagittal view of a rodent brain highlighting the two neurogenic
zones of the adult mammalian brain
Fig.2: Overview of physiological and environmental modulation of Adult Hippocampal
Neurogenesis and its impact on Learning & Memory abilities and Mood. The doted squares
contain the enlarged hippocampus. The red dots symbolize newborn neurons in the dentate
gyrus (DG) (Stangl & Thuret, 2009).

DetectionofproliferationindenategyrysC57BL6Mice Detection of proliferation and neurogenesis

in the dentate gyrus of C57BL/6 mice. Confocal images of dividing BrdU-positive cells in the
dentate gyrus. Sagittal sections were imuunostained and double labeled for BrdU (green) and
the neuronal marker NeuN (red). New-born/dividing neurons appear in yellow. d, e, f are higher
magnification of the boxed area in a, b, c respectively (From Thuret et. al, 2009)
-> CELLS AND BEHAVIOUR
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