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Minimal behavioral effects from developmental cerebellar stunting in young rats induced by postnatal treatment with
A M Cada1, E P Gray, S A Ferguson
1Division of Neurotoxicology, National Center for Toxicological Research/FDA, 72079, Jefferson, AR, USA.
Insights
Postnatal treatment with alpha-difluoromethylornithine (DFMO) impacts rat cerebellar development. Despite dose-dependent changes in brain weight ratios and delayed eye opening, early behavioral assessments showed no significant effects.
Area of Science:
- Neuroscience
- Developmental Biology
- Pharmacology
Background:
- Polyamines are crucial for growth and development.
- Alpha-difluoromethylornithine (DFMO) inhibits ornithine decarboxylase, reducing polyamine levels.
- DFMO treatment can impact body and brain development.
Purpose of the Study:
- To investigate the effects of early postnatal DFMO treatment on rat development and behavior.
- To assess the impact of DFMO on brain weight ratios and eye opening.
- To evaluate early behavioral performance following DFMO administration.
Main Methods:
- Rats received DFMO (0-750 mg/kg) subcutaneously on postnatal days 5-10.
- Behavioral tests included righting reflex, negative geotaxis, forelimb hanging, open field, and rotarod.
- Brain weights and eye opening were assessed on postnatal day 28.
Main Results:
- DFMO decreased the cerebellar/whole-brain ratio dose-dependently.
- The frontal cortex/whole-brain ratio increased with DFMO treatment.
- Eye opening was delayed in all DFMO-treated groups; body weight was unaffected.
- No significant effects were observed in the assessed early behaviors.
Conclusions:
- Early postnatal DFMO treatment significantly impacts cerebellar development.
- Observed cerebellar changes did not lead to apparent behavioral deficits in early development.
- Potential long-term behavioral alterations may emerge in adulthood.
Abstract:
Postnatal treatment with alpha-difluoromethylornithine (DFMO), a potent inhibitor of ornithine decarboxylase, reduces polyamine levels in rats. Because polyamines are critically involved in growth and development, body and/or brain weights are often decreased by DFMO treatment. Here, rats were injected subcutaneously with 0, 250, 500, or 750 mg/kg of DFMO on postnatal days (PNDs) 5-10. Behavioral assessments included righting reflex, negative geotaxis, forelimb hanging, open field activity, and rotarod performance. Additionally, day of eye opening was recorded and on PND 28, whole and regional brain weights were measured. Cerebellar/whole-brain ratio was decreased in a dose-dependent manner whereas frontal cortex/whole-brain ratio was increased. Eye opening was delayed to a similar extent in all treated groups whereas body weight was unaffected. alpha-difluoromethylornithine treatment had no significant effects on the assessed behaviors. These results indicate that 6 days of DFMO treatment can substantially impact cerebellar development, but this appears to have few effects on these early assessed behaviors. However, potential behavioral alterations may not be apparent until adulthood. Published by Elsevier Science Inc.