Regional difference in the neurotoxicity of ochratoxin A on the developing cerebral cortex in mice

Pregnant mice were treated intraperitoneally with 3 mg/kg of ochratoxin A on day 10 of gestation. They were allowed to give birth and the offspring were killed at 6 weeks of age for observation. Prenatal exposure to ochratoxin A caused microcephaly in offspring. Their body weight, brain weight, cortical thickness and numerical densities of neurons and synapses in somatosensory and visual cortex were examined. The mice exposed in utero to ochratoxin A showed a significant deficit in brain weight compared to the age-matched control, but there was no significant difference in body weight between these two groups. The cortical thickness showed a significant decrease in both somatosensory and visual cortex. Normal control mice had about 66,000 neurons/mm3, while age-matched ochratoxin A-treated mice had about 91,000 neurons/mm3 in somatosensory cortex. There was a significant increase in OA-treated group. However, there was no significant difference in the numerical density of neurons in visual cortex. On the other hand, there was no significant difference in the numerical density of synapses in both somatosensory and visual cortex. The somatosensory cortex of control mice had about 13,000 synapses per neuron, whereas ochratoxin A-treated mice had about 9,400 synapses per neuron. In the visual cortex, no significant difference was seen in synapse-to-neuron ratios. The discrepancy in the numerical density of neurons and synapse-to-neuron ratios between the somatosensory and visual cortex might derive from a time difference in cortical neurogenesis.