Bromodeoxyuridine and methylazoxymethanol exposure during brain development affects behavior in rats: consideration for a role of nerve growth factor and brain derived neurotrophic factor.
Rats prenatally exposed to the neurotoxins methylazoxymethanol (MAM) or 5-Bromo-2'-deoxyuridine (BrdU) are used as animal models of brain maldevelopment. We administered in rats MAM (20 mg/kg), or BrdU (100 mg/kg) or both at gestational day 11. Locomotion was not affected by any prenatal treatment whereas learning was delayed in the Morris maze in MAM animals. BrdU induced decreased NGF and BDNF levels in the hippocampus. In the parietal cortex prenatal BrdU administration induced NGF potentation associated with decreased BDNF. Animals treated with both MAM and BrdU showed also an increased immunopositivity for choline acetyltransferase (ChAT) and low affinity neurotrophins' receptor (p75) in the septum and Meynert's nuclei. These findings suggest that embryonic exposure to MAM and/or BrdU may be useful for studying mechanisms associated with neurodegenerative diseases affecting brain morphology and behavior.
Fiore
M
M
Department of Biological Psychiatry, University of Groningen, Hanzeplein 1, 9713 EZ Groningen, The Netherlands.
Aloe
L
L
Westenbroek
C
C
Amendola
T
T
Antonelli
A
A
Korf
J
J
D000818:Animals; D000963:Antimetabolites / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000196:embryology* / Q000378:metabolism; D001923:Brain Chemistry / Q000187:drug effects; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D001973:Bromodeoxyuridine / Q000494:pharmacology*; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D005260:Female; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D001523:Mental Disorders / Q000378:metabolism; D008746:Methylazoxymethanol Acetate / Q000031:analogs & derivatives / Q000494:pharmacology*; D020932:Nerve Growth Factor / Q000378:metabolism*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D020800:Receptor, Nerve Growth Factor / Q000378:metabolism; D013723:Teratogens / Q000494:pharmacology*
D000963:Antimetabolites; D019208:Brain-Derived Neurotrophic Factor; D020800:Receptor, Nerve Growth Factor; D013723:Teratogens; D008746:Methylazoxymethanol Acetate; D020932:Nerve Growth Factor; D002795:Choline O-Acetyltransferase; D001973:Bromodeoxyuridine; C030667:methylazoxymethanol