PMID- 17142008 OWN - NLM STAT- MEDLINE DCOM- 20070601 LR - 20161124 IS - 0892-0362 (Print) IS - 0892-0362 (Linking) VI - 29 IP - 2 DP - 2007 Mar-Apr TI - Exposure in fetus of methylazoxymethanol in the rat alters brain neurotrophins' levels and brain cells' proliferation. PG - 273-81 AB - 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. FAU - Di Fausto, Veronica AU - Di Fausto V AD - Institute of Neurobiology and Molecular Medicine, CNR-EBRI Via del Fosso di Fiorano, 64, 00143 Rome, Italy. FAU - Fiore, Marco AU - Fiore M FAU - Aloe, Luigi AU - Aloe L LA - eng PT - Journal Article DEP - 20061028 PL - United States TA - Neurotoxicol Teratol JT - Neurotoxicology and teratology JID - 8709538 RN - 0 (Nerve Growth Factors) RN - 0 (Teratogens) RN - 592-62-1 (Methylazoxymethanol Acetate) RN - EC 2.7.10.1 (Receptor, trkA) RN - EC 2.7.10.1 (Receptor, trkB) RN - G34N38R2N1 (Bromodeoxyuridine) RN - JGG19N3YDQ (methylazoxymethanol) SB - IM MH - Analysis of Variance MH - Animals MH - Brain/cytology/*drug effects/metabolism MH - Bromodeoxyuridine/metabolism MH - Cell Count/methods MH - Cell Proliferation/*drug effects MH - *Embryo, Mammalian/cytology/drug effects/metabolism MH - Female MH - Methylazoxymethanol Acetate/*analogs & derivatives/pharmacology MH - Nerve Growth Factors/classification/*metabolism MH - Pregnancy MH - Rats MH - Receptor, trkA/metabolism MH - Receptor, trkB/metabolism MH - Teratogens/*pharmacology EDAT- 2006/12/05 09:00 MHDA- 2007/06/02 09:00 CRDT- 2006/12/05 09:00 PHST- 2006/04/13 00:00 [received] PHST- 2006/10/12 00:00 [revised] PHST- 2006/10/22 00:00 [accepted] PHST- 2006/12/05 09:00 [pubmed] PHST- 2007/06/02 09:00 [medline] PHST- 2006/12/05 09:00 [entrez] AID - S0892-0362(06)00143-7 [pii] AID - 10.1016/j.ntt.2006.10.007 [doi] PST - ppublish SO - Neurotoxicol Teratol. 2007 Mar-Apr;29(2):273-81. doi: 10.1016/j.ntt.2006.10.007. Epub 2006 Oct 28.