Exposure in fetus of methylazoxymethanol in the rat alters brain neurotrophins' levels and brain cells' proliferation
Institute of Neurobiology and Molecular Medicine, CNR-EBRI Via del Fosso di Fiorano, 64, 00143 Rome, Italy. Neurotoxicology and Teratology
(Impact Factor: 2.76).
03/2007; 29(2):273-81. DOI: 10.1016/j.ntt.2006.10.007
Changes during gestation have been shown to induce brain maldevelopment associated with changes in neurotrophins as nerve growth factor (NGF), brain derived neurotrophic factor (BDNF) and neuropsychiatric disorders in humans. A rat model of altered prenatal brain development resembling the onset of schizophrenia has been obtained by administering in fetus methylazoxymethanol (MAM) at gestational day 12 which impairs the growth of limbic pathways between the entorhinal cortex and the hippocampus. Using the MAM model we studied in young rats the brain levels of both NGF/BDNF and their main receptors, TrkA/TrkB, to investigate whether or not changes in neurotrophins could affect the presence of brain BrdU positive cells. We found increased NGF and BDNF protein levels, associated with elevated TrkA and TrkB expression, in the hippocampus, entorhinal cortex, olfactory lobes and subventricular zone (SVZ), brain areas playing a key role in the production and migration of new dividing cells. We also found higher levels of BrdU positive cells in the SVZ and hippocampus but not a significant potentiation in the entorhinal cortex and olfactory lobes. All together the findings indicate that prenatal MAM exposure in young rats may elicit both neurotrophins' elevation and cell proliferation in limbic brain areas.
Available from: Jeremy Barry
- "With hippocampal volumes, enriched animals did not increase at a higher rate than non-enriched, but MAM animals did increase faster than controls. This may reflect a form of compensatory neurogenesis, as hypothesized in an E12 MAM exposure model , and a promising demonstration that the brain is plastic and imbued with the capacity to recover, at least in part, from early life damage. "
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ABSTRACT: Children with malformations of cortical development (MCD) frequently have associated cognitive impairments which reduce quality of life. We hypothesized that cognitive deficits associated with MCD can be improved with environmental manipulation or additional training. The E17 methylazoxymethanol acetate (MAM) exposure model bears many anatomical hallmarks seen in human MCDs as well as similar behavioral and cognitive deficits. We divided control and MAM exposed Sprague-Dawley rats into enriched and non-enriched groups and tested performance in the Morris water maze. Another group similarly divided underwent sociability testing and also underwent Magnetic Resonance Imaging (MRI) scans pre and post enrichment. A third group of control and MAM rats without enrichment were trained until they reached criterion on the place avoidance task. MAM rats had impaired performance on spatial tasks and enrichment improved performance of both control and MAM animals. Although MAM rats did not have a deficit in sociability they showed similar improvement with enrichment as controls. MRI revealed a whole brain volume decrease with MAM exposure, and an increase in both MAM and control enriched volumes in comparison to non-enriched animals. In the place avoidance task, MAM rats required approximately 3 times as long to reach criterion as control animals, but with additional training were able to reach control performance. Environmental manipulation and additional training can improve cognition in a rodent MCD model. We therefore suggest that patients with MCD may benefit from appropriate alterations in educational strategies, social interaction and environment. These factors should be considered in therapeutic strategies.
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ABSTRACT: Four basic estimation methods are discussed, namely the
delay-advance method, the early-late filter method, a modified
early-late filter method, and the novel two-tone method. These methods
all use noise power estimation in a frequency bin not occupied by a
signal; this estimate is then used to reduce the bias and make the
estimate of the time error consistent. Simulation results on the
performance of these four methods obtained using the bias reduction (BR)
technique are given. The simulation results are for AWGN (additive white
Gaussian noise) only, which represents system noise and noise jamming
across the entire band. The BR technique is shown to reduce the bias and
make the estimates consistent for all four basic methods. Although the
BR also increases the standard deviation, the decrease in bias more than
offsets the effect of increased standard deviation. The best overall
performance is achieved with the modified early-late filter method
Available from: Marco Fiore
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ABSTRACT: Rats exposed during prenatal life to methylazoxymethanol (MAM) display in postnatal age structural and behavioral deficits resembling those observed in schizophrenic patients. These deficits are associated with significant changes in brain nerve growth factor (NGF) and brain derived neurotrophic factor (BDNF), particularly in the hippocampus and entorhinal cortex. In the present study, we used the MAM model to investigate in young rats the effect of antipsychotics, Clozapine and Haloperidol, on brain and blood NGF and BDNF presence. Young animals were used because administration of antipsychotics during adolescence is a common feature of intervention. The results showed that administration of Clozapine and Haloperidol causes significant changes in the concentration of NGF and BDNF in the brain and bloodstream of MAM-treated rats. These findings indicate that these drugs may affect the synthesis and release of neurotrophins in the central nervous system and in the blood circulation. In addition, the MAM model can be a useful tool to investigate the biochemical and molecular mechanisms regarding the effects of antipsychotics.
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