Team 'Neurogenesis and pathophysiology', manager: Nora Abrous, PhD.
The discovery that neurogenesis occurs in discrete regions of the adult mammalian brain, including human's, such as the dentate gyrus (DG) of the hippocampal formation (HF), has stimulated the interest of the scientific community. Indeed, this structure is involved in memory processes and is vulnerable to the effect of aging, stress, and addiction.
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We have studied the physiological significance of hippocampal neurogenesis and its involvement in pathological behaviors.We had shown the existence of a reciprocal relationship between neurogenesis and spatial memory (I) and that neoneurons are involved in the physiopathology of memory (II).
I. RECIPROCICAL RELATIONSHIP BETWEEN NEUROGENESIS AND SPACIAL MEMORY
We had shown that:
A) Matures neoneurons are necessary learning and memory
 Spatial memory is evaluated in the water maze |
1. The neoneurons production is correlated to spatial memory abilities in senescent rats.
 Drapeau & al., 2003 2. blocking the production of neoneurons in a transgenic model drives to deficiency in the spatial memory  Dupret & al., 2008 |
B) Spatial learning regulates neurogenesis and selects a precise population of immature neoneurons of which it increases the survival. This new phenomenon, reminding the process of selective stabilization observed during the development, is involved in the process of memorization since its alteration leads to memory disorders in adult and some old subjects.
Homeostatic regulation of neoneurons numbers
Döbrössy & al., 2003 Dupret & al., 2007 Drapeau & al., 2007 Learning increases the survival of oldest immature neoneurons to the detriment of youngest immature neoneurons |
Regulation of dentritic arbor of neoneurons selected by learning
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II. NEONEURONS ARE INVOLVED IN THE PATHOPHYSIOPATHOLGY OF MEMORY
During the development, there are "critic periods" during which the genetic program of development is sensitive to environmental influences. One of them, the prenatal period is sensitive to manipulations of maternal environment. It had been shown that the exposition of the mother to a stressful environment during the gestation disturbs the development of the offspring. These deleterious influences accelerate that apparition of age-related memory disorders.
We had shown that prenatal stress decreases adult neurogenesis all along the lifetime and leads to memory impairment in the water maze (Lemaire & al., 2000). These alterations are associated to a hyperactivity of HPA axis.
A gestational stress during the last week of gestation decreases adult neurogenesis of male offspring. These effects are observed from adolescence and last until senescence (Lemaire & al., 2006).
The effects of a prenatal stress are reversible and involve the modification of the postnatal environment (Lemaire & al., 2006).
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The manipulation of young rats during the first weeks of life (Handling=H) allows to abrogate the deleterious effects of a prenatal stress (PS) on the adult neurogenesis. These effects last until senescence (Lemaire & al., 2006). |
These results show that a prenatal stress causes a hyperactivity of the HPA axis which lows adult neurogenesis and accelerates the occurrence of age-related memory disorders. On the contrary, enriching experiments favor a successful ageing in increasing the production of new neurons. These results reinforce the hypothesis that numerous disorders have their origins in early periods of development.
Composition table of the team
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