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Muriel KOEHL

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47 publication(s) depuis Juin 1997:

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07/2008 | Faseb J   IF 5.4
Exercise-induced promotion of hippocampal cell proliferation requires beta-endorphin.
Koehl M, Meerlo P, Gonzales D, Rontal A, Turek FW, Abrous DN

Adult hippocampal neurogenesis is influenced by a variety of stimuli, including exercise, but the mechanisms by which running affects neurogenesis are not yet fully understood. Because beta-endorphin, which is released in response to exercise, increases cell proliferation in vitro, we hypothesized that it could exert a similar effect in vivo and mediate the stimulatory effects of running on neurogenesis. We thus analyzed the effects of voluntary wheel-running on adult neurogenesis (proliferation, differentiation, survival/death) in wild-type and beta-endorphin-deficient mice. In wild-type mice, exercise promoted cell proliferation evaluated by sacrificing animals 24 h after the last 5-bromo-2'-deoxyuridine (BrdU) pulse and by using endogenous cell cycle markers (Ki67 and pH(3)). This was accompanied by an increased survival of 4-wk-old BrdU-labeled cells, leading to a net increase of neurogenesis. Beta-endorphin deficiency had no effect in sedentary mice, but it completely blocked the running-induced increase in cell proliferation; this blockade was accompanied by an increased survival of 4-wk-old cells and a decreased cell death. Altogether, adult neurogenesis was increased in response to exercise in knockout mice. We conclude that beta-endorphin released during running is a key factor for exercise-induced cell proliferation and that a homeostatic balance may regulate the final number of new neurons.

03/2008 | Genes Brain Behav   IF 3.2
Impact of intra- and interstrain cross-fostering on mouse maternal care.
van der Veen R, Abrous DN, de Kloet ER, Piazza PV, Koehl M

The importance of maternal care in shaping an individual's phenotype in health and disease is becoming more and more apparent in both human and animal studies. However, in mouse studies using inbred strains or knockout mice to analyze the genetic influences on the development of normal and aberrant behavioral phenotypes, maternal behavior is very poorly characterized and often ignored. This study provides an extensive analysis of spontaneous maternal behavior of inbred mice in three conditions: (1) comparing two commonly used strains, (2) analyzing the impact of adopting pups from the same strain (intrastrain cross-fostering) and (3) analyzing the impact of adopting pups from a different strain (interstrain cross-fostering). For each condition, maternal behavior was analyzed continuously over 23-h periods on postnatal days 2, 4, 6 and 9. We report that (1) the maternal behavior of C57BL/6J and DBA/2J dams toward their biological offspring is highly similar, (2) intrastrain cross-fostering has minimal impact on maternal behavior of C57BL/6J and DBA/2J dams, (3) interstrain cross-fostering does not modify the strain differences in maternal care observed between AKR and C3H/He mothers and (4) the pup strain does influence the amount of maternal behavior shown by both mothers in interstrain cross-fostering. These latter findings demonstrate that both mother strain and pup strain are key determinants of maternal behavior.

2008 | PLoS ONE   IF 2.8
Spatial relational memory requires hippocampal adult neurogenesis.
Dupret D, Revest JM, Koehl M, Ichas F, De Giorgi F, Costet P, Abrous DN, Piazza PV

The dentate gyrus of the hippocampus is one of the few regions of the mammalian brain where new neurons are generated throughout adulthood. This adult neurogenesis has been proposed as a novel mechanism that mediates spatial memory. However, data showing a causal relationship between neurogenesis and spatial memory are controversial. Here, we developed an inducible transgenic strategy allowing specific ablation of adult-born hippocampal neurons. This resulted in an impairment of spatial relational memory, which supports a capacity for flexible, inferential memory expression. In contrast, less complex forms of spatial knowledge were unaltered. These findings demonstrate that adult-born neurons are necessary for complex forms of hippocampus-mediated learning.

2008 | PLoS ONE   IF 2.8
Maternal environment influences cocaine intake in adulthood in a genotype-dependent manner.
van der Veen R, Koehl M, Abrous DN, de Kloet ER, Piazza PV, Deroche-Gamonet V

BACKGROUND: Accumulating epidemiological evidence points to the role of genetic background as a modulator of the capacity of adverse early experiences to give rise to mental illness. However, direct evidence of such gene-environment interaction in the context of substance abuse is scarce. In the present study we investigated whether the impact of early life experiences on cocaine intake in adulthood depends on genetic background. In addition, we studied other behavioral dimensions associated with drug abuse, i.e. anxiety- and depression-related behaviors. METHODOLOGY/PRINCIPAL FINDINGS: For this purpose, we manipulated the maternal environment of two inbred mouse strains, the C57BL/6J and DBA/2J by fostering them with non-related mothers, i.e. the C3H/HeN and AKR strains. These mother strains show respectively high and low pup-oriented behavior. As adults, C57BL/6J and DBA/2J were tested either for cocaine intravenous self-administration or in the elevated plus-maze and forced swim test (FST). We found that the impact of maternal environment on cocaine use and a depression-related behavior depends upon genotype, as cocaine self-administration and behavior in the FST were influenced by maternal environment in DBA/2J, but not in C57BL/6J mice. Anxiety was not influenced by maternal environment in either strain. CONCLUSIONS/SIGNIFICANCE: Our experimental approach could contribute to the identification of the psychobiological factors determining the susceptibility or the resilience of certain individuals to develop psychopathologies.


STUDY OBJECTIVES: Numerous clinical studies and sleep surveys have shown pronounced sex differences in the occurrence of insomnia and other sleep pathologies. It has been suggested that sex differences in sleep, while subtle under baseline conditions, may increase in magnitude under biological or environmental challenges. However, controlled and experimental studies on sleep under challenged conditions rarely include female subjects. In this context, we examined sex differences in sleep in the mouse, not only under baseline conditions, but also after sleep deprivation and restraint stress. DESIGN: Adult male and female C57BL/6J mice were implanted with electrodes to record sleep-wake architecture and sleep electroencephalogram under baseline conditions and after 6 hours of sleep deprivation or 1 hour of restraint stress at the beginning of the daily light phase. RESULTS: Although baseline sleep patterns slightly differed between the sexes, the homeostatic recovery response to sleep deprivation was similar. In contrast, the changes in sleep after restraint stress were markedly different between male and female mice, with males displaying a stronger initial suppression of sleep and a stronger rebound of rapid-eye-movement sleep later in the recovery phase. CONCLUSIONS: In mice, the fundamental homeostatic properties of sleep regulation may not differ between the sexes, but the way sleep is affected and disrupted by environmental influences may be sex dependent. The latter may reflect sex differences in stress sensitivity.

04/2005 | Physiol Rev   IF 24.3
Adult neurogenesis: from precursors to network and physiology.
Abrous DN, Koehl M, Le Moal M

The discovery that the adult mammalian brain creates new neurons from pools of stemlike cells was a breakthrough in neuroscience. Interestingly, this particular new form of structural brain plasticity seems specific to discrete brain regions, and most investigations concern the subventricular zone (SVZ) and the dentate gyrus (DG) of the hippocampal formation (HF). Overall, two main lines of research have emerged over the last two decades: the first aims to understand the fundamental biological properties of neural stemlike cells (and their progeny) and the integration of the newly born neurons into preexisting networks, while the second focuses on understanding its relevance in brain functioning, which has been more extensively approached in the DG. Here, we propose an overview of the current knowledge on adult neurogenesis and its functional relevance for the adult brain. We first present an analysis of the methodological issues that have hampered progress in this field and describe the main neurogenic sites with their specificities. We will see that despite considerable progress, the levels of anatomic and functional integration of the newly born neurons within the host circuitry have yet to be elucidated. Then the intracellular mechanisms controlling neuronal fate are presented briefly, along with the extrinsic factors that regulate adult neurogenesis. We will see that a growing list of epigenetic factors that display a specificity of action depending on the neurogenic site under consideration has been identified. Finally, we review the progress accomplished in implicating neurogenesis in hippocampal functioning under physiological conditions and in the development of hippocampal-related pathologies such as epilepsy, mood disorders, and addiction. This constitutes a necessary step in promoting the development of therapeutic strategies.

01/08/2004 | Sleep   IF 4.6
Effects of gamma-hydroxybutyrate (GHB) on vigilance states and EEG in mice.
Meerlo P, Westerveld P, Turek FW, Koehl M

STUDY OBJECTIVES: Gamma-hydroxybutyrate (GHB) is an endogenous neuromodulator that appears to have wide-ranging effects on vigilance and behavior. In the present study, we examined the effects of GHB on sleep-wake behavior and EEG in mice. In addition, we measured effects of GHB on body temperature and arousal or stress hormones. DESIGN: Adult male BALB/c mice were implanted with electroencephalographic and electromyographic electrodes to record vigilance states and an intraperitoneal transmitter to record body temperature. After recovery from surgery and habituation to the recording procedure, the mice were intraperitoneally injected with saline or GHB (50, 150 or 250 mg/kg) half an hour after light onset. Blood samples to measure effects of GHB on corticosterone and prolactin levels were collected in a separate group of mice. SETTING: N/A PATIENTS: N/A INTERVENTIONS: N/A RESULTS: At the lowest dose, GHB had no conspicuous effects on behavioral vigilance and electroencephalogram, nor on body temperature and endocrine measures. At the 2 higher doses, GHB induced a short period of electroencephalographic hypersynchrony in parallel to complete behavioral inactivity, an unnatural flat body posture, and nonresponsiveness to stimulation. After the highest dose of GHB, this state of reduced vigilance was associated with a decrease in body temperature, while prolactin and corticosterone levels were strongly increased. CONCLUSIONS: The results do not indicate a clear sleep-promoting effect of GHB in mice, but, at higher doses, it caused electroencephalographic hypersynchronization together with a coma-like state.

06/2004 | Behav Neurosci   IF 2.1
Early and later adoptions differently modify mother-pup interactions.
Darnaudery M, Koehl M, Barbazanges A, Cabib S, Le Moal M, Maccari S

Life events occurring during the perinatal period have strong long-term effects. In rats, prenatal stress, postnatal maternal separations, or adoptions at different periods are known to affect behavior and reactivity to stress in offspring. To determine the role of maternal factors on differential outcome adoptions, the authors investigated interactions between pups and the adopting mothers by assessing both pups' ultrasound emissions and maternal behavior. Early and late adoptions increased mother care at the moment of adoption and during mother-infant reunion after a separation procedure. However, although early adoption induced a decrease in pups' ultrasound emissions in response to a stressful separation, later adoptions enhanced it. Results suggest a sensitive period during which fostering may change pups' and dams' behavior.

2004 | Neurotox Res   IF 3.3
Environmentally induced long-term structural changes: cues for functional orientation and vulnerabilities.
Montaron MF, Koehl M, Lemaire V, Drapeau E, Abrous DN, Le Moal M

Environmental challenges profoundly modify phenotypes and disrupt inherent developmental programs both at functional and structural levels. As an example, we have studied the impact of these environmental influences on adult neurogenesis in the dentate gyrus. Neurogenesis results from an inherent program, participates to hippocampal network organization and, as a consequence, to the various functional abilities depending on this region, including memories. In preclinical studies of aging we have shown that phenotypes vulnerable to the development of spatial memory disorders are characterized by lower hippocampal neurogenesis. We have hypothesized that these interindividual variations in functional expression of neurogenesis in senescent subjects could be predicted early in life. Indeed, a behavioral response (novelty-induced locomotor reactivity) and a biological trait (hypothalamo-pituitary-adrenal axis activity), which are predictive of cognitive impairments later in life, are related to neurogenesis in young adult rats. This suggests that subjects starting off with an impaired neurogenesis, here rats that are high reactive to stress, are predisposed for the development of age-related cognitive disorders. We have further shown that these inter-individual differences result from early deleterious life events. Indeed, prenatal stress orients neurogenesis in pathological ways for the entire life, and precipitates age-related cognitive impairments. Altogether these data suggest first that hippocampal neurogenesis plays a pivotal role in environmentally-induced vulnerability to the development of pathological aging, and second that environmental challenges and life events orient structural developments, leading to different phenotypes.