Behavioral consequences of interference with CNS development in the early fetal period
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Abstract:
As a part of a series of investigations into the structural and functional consequences of interference with cell proliferation, mice were treated with 5-azacytidine during two stages of early fetal life. Treatment on either the twelfth or fourteenth day of gestation led to permanent significant reductions in body weight and brain weight. Behaviorally, the earlier treatment was associated with a delay in development of the righting reflex, permanent deficits in locomotor coordination, and hypoactivity. Treatment on the fourteenth day of gestation led to decreased passive avoidance, increased active avoidance, and hyperactivity--the same syndrome observed after treatment on the eighteenth day. Both treatments led to abnormal behavior on a spatial maze task. The developmental outcome of injuries induced in the early fetal period appears similar to the outcome of injuries at later stages of development.
Insights
5-azacytidine exposure during early mouse gestation permanently reduced body and brain weight. Developmental effects, including behavioral deficits, were observed, suggesting similar outcomes from early versus later fetal developmental injuries.
Area of Science:
- Developmental toxicology
- Neuroscience
- Teratology
Background:
- Cell proliferation is crucial for normal fetal development.
- Interference with cell proliferation can lead to structural and functional abnormalities.
- Understanding the consequences of early developmental insults is vital for predicting long-term outcomes.
Purpose of the Study:
- To investigate the structural and functional consequences of 5-azacytidine exposure during early mouse fetal development.
- To compare the effects of 5-azacytidine treatment at different gestational ages.
- To assess the long-term behavioral and physical outcomes following early fetal exposure.
Main Methods:
- Pregnant mice were administered 5-azacytidine on gestational days 12 or 14.
- Body weight and brain weight were measured postnatally.
- Behavioral assessments included righting reflex, locomotor coordination, passive and active avoidance, and spatial maze performance.
Main Results:
- Treatment on gestational days 12 or 14 resulted in permanent reductions in body and brain weight.
- Early treatment (day 12) caused delayed righting reflex, impaired locomotor coordination, and hypoactivity.
- Later treatment (day 14) induced decreased passive avoidance, increased active avoidance, hyperactivity, and abnormal spatial maze behavior.
Conclusions:
- 5-azacytidine exposure during critical early fetal periods induces significant and permanent physical and behavioral deficits.
- The developmental outcomes of early fetal injuries appear comparable to those induced at later developmental stages.
- This study highlights the vulnerability of the developing nervous system to teratogenic agents.