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Impaired Biel and radial arm maze learning in rats with methylnitrosourea-induced microcephaly
1Pharma Research and Development Division, Hoechst Japan Limited, Saitama.
Abstract:
Jc1:SD rats were given methylnitrosourea (MNU; 5 mg/kg, IP) on day 13 of gestation. Male offspring with MNU-induced microcephaly were examined on the Biel water maze and its mirror-image maze at 6 weeks of age and on a radial eight-arm maze at 14 weeks of age. The MNU rats showed postnatal depression in body weight. Their brain weight was about 60% of the control value, and they were thus microcephalic. The MNU animals made significantly more errors on the Biel maze and its mirror-image maze than the controls. In the radial arm maze test, they required more trials to acquire the learning criterion than the controls, and the animals with the acquired learning criterion were fewer. In the retest, however, no significant difference appeared in number of trials required for reacquisition of the criterion between the MNU and control animals. The autopsy of the MNU animals revealed the thinned cerebral cortex and hypoplastic hippocampus. The present results with the MNU rats confirmed the learning impairment and suggested no effect of microcephaly on retention of the acquired memory.
Insights
Methylnitrosourea (MNU) exposure in pregnant rats caused microcephaly in male offspring, leading to significant learning impairments. However, microcephaly did not affect the retention of previously acquired memories.
Area of Science:
- Neuroscience
- Developmental Biology
- Toxicology
Background:
- Methylnitrosourea (MNU) is a known teratogen.
- MNU-induced microcephaly can serve as a model for studying neurodevelopmental disorders.
Purpose of the Study:
- To investigate the cognitive effects of MNU-induced microcephaly in a rat model.
- To assess learning and memory retention in microcephalic rats.
Main Methods:
- Pregnant Sprague-Dawley rats were administered MNU on day 13 of gestation.
- Male offspring with induced microcephaly were tested on the Biel water maze and radial eight-arm maze.
- Brain weight, body weight, and histological changes were analyzed post-mortem.
Main Results:
- MNU-exposed rats exhibited microcephaly, with brain weight approximately 60% of controls.
- Microcephalic rats showed significantly more errors on spatial learning tasks (Biel and radial arm mazes).
- While initial learning was impaired, retesting revealed no significant difference in memory retention compared to controls.
Conclusions:
- MNU-induced microcephaly in rats is associated with significant learning deficits.
- The study suggests that microcephaly does not impair the retention of acquired memories.
- This model provides insights into the cognitive consequences of prenatal exposure to neurotoxic agents.