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Neurochemical effects of prenatal treatment with ochratoxin A on fetal and adult mouse brain

Abstract

Ochratoxin A (OA) is a mycotoxin produced by several storage fungi, such asAspergillus ochraceus and severalPenicillium species. OA (3 mg/kg) was given intraperitoneally to pregnant mice on day 11 of gestation (day 1=day of insemination), and neurochemical changes in brains of their offspring were examined at fetal and adult stages. OA treatment produced retardation of intrauterine growth as well as microencephaly and reductions in total weight and DNA content of fetal brains. Specific activities of lysosomal enzymes in fetal brains began to increase by the 2nd day after treatment and to reach peak activities by the 3rd or 4th day after injection, indicative of cell dealth in the developing brains. Examination of brain regions of offspring three months after birth revealed that both tissue weight and DNA content were reduced to 80% of control in cerebral hemispheres (CHs; cerebral cortex and subjacent white matter, hippocampus, and amygdala) and to 90% of control in remainder of the brain (BGDM; basal ganglia, diencephalon, and mesencephalon). Total content of noradrenaline (NA), dopamine (DA) 5-hydroxytryptamine (5-HT) in treated CH showed about 15% reduction, although, expressed on a tissue weight basis, concentrations of these monoamines were increased by about 15%. Total DA content in BGDM was also reduced to 85% of controls, but total content of NA and 5-HT in BGDM and pons-medulla oblongata did not change. These result suggest that synaptogenesis of monoamine neurons in the cerebrum is imparied by prenatal treatment with OA, and that dopaminergic neurons show a slight selective vulnerability to the toxin.

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Abbreviations

(OA):

Ochratoxin A

(CH):

cerebral hemisphere

(BGDM):

remainder of the brain consisting basal ganglia, diencephalon and mesencephalon

(PM):

pons-medulla oblongata

(CE):

cerebellum

(NA):

noradrenaline

(DA):

dopamine

(5-HT):

5-hydroxytryptamine

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Tamaru, M., Hirata, Y. & Matsutani, T. Neurochemical effects of prenatal treatment with ochratoxin A on fetal and adult mouse brain. Neurochem Res 13, 1139–1147 (1988). https://doi.org/10.1007/BF00971631

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  • DOI: https://doi.org/10.1007/BF00971631

Key Words

  • Ochratoxin A
  • tetal brains
  • microencephalic mice
  • lysosomal enzymes
  • DNA content