title: Long-lasting effects of prenatal MAM treatment on water maze performance in rats: associations with altered brain development and neurotrophin levels.
abstract: We previously reported that prenatal methylazoxymethanol (MAM) administered on days 11 and 12 of rat pregnancy induces structural changes in the cytoarchitecture of the hippocampal-entorhinal axis. We also showed that young and middle-aged prenatally treated MAM animals displayed changes in brain neurotrophin levels [Neurosci. Lett. 309 (2001) 113; Physiol. Behav. 71 (2000) 57.]. To continue this line of investigation, the working hypothesis adopted was that prenatal MAM administration, by interfering with limbic neurogenesis, could impair learning and memory ability of aged animals in the water maze. It was found that injection of MAM during early rat brain development induced deficits in both the acquisition and retention phases of the Morris maze. These behavioral changes were associated with significant changes in brain nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF), reduced choline acetyltransferase (ChAT) immunoreactivity in forebrain cholinergic neurons and loss of neuropeptide Y (NPY) immunodistribution in cells of the entorhinal cortex. This finding, as well as confirming previous studies showing that injection of prenatal MAM administration induces significant changes in hippocampal-entorhinal axis neurogenesis and marked behavioral deficits in adult life, provides additional experimental evidence supporting the hypothesis that loss of NGF and/or BDNF-receptive or producing cells can co-occur at the onset of neurodevelopmental disorders.
authors.affiliation: Istituto di Neurobiologia e Medicina Molecolare, CNR, Viale Marx, 43/15, 00137 Rome, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Fiore
authors.forename: Jakob
authors.initials: J
authors.lastname: Korf
authors.forename: Alessia
authors.initials: A
authors.lastname: Antonelli
authors.forename: Lucia
authors.initials: L
authors.lastname: Talamini
authors.forename: Luigi
authors.initials: L
authors.lastname: Aloe
mesh_terms: D000818:Animals; D001479:Basal Ganglia / Q000378:metabolism; D001921:Brain / Q000254:growth & development / Q000378:metabolism*; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D018728:Entorhinal Cortex / Q000166:cytology / Q000378:metabolism; D005260:Female; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism; D007150:Immunohistochemistry; D018782:Maze Learning / Q000187:drug effects*; D008746:Methylazoxymethanol Acetate / Q000031:analogs & derivatives* / Q000633:toxicity*; D020932:Nerve Growth Factor / Q000378:metabolism*; D009474:Neurons / Q000201:enzymology; D009478:Neuropeptide Y / Q000378:metabolism; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D017208:Rats, Wistar; D013723:Teratogens / Q000633:toxicity*
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D009478:Neuropeptide Y; D013723:Teratogens; D008746:Methylazoxymethanol Acetate; D020932:Nerve Growth Factor; D002795:Choline O-Acetyltransferase; C030667:methylazoxymethanol