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Published on: December 4, 2013
Sodium valproate exposure during the brain growth spurt transiently impairs spatial learning in prepubertal rats
Cláudio C Filgueiras1, Fernanda Pohl-Guimarães, Thomas E Krahe
1Departamento de Ciências Fisiológicas, Universidade do Estado do Rio de Janeiro, Brazil. ccfilg@pq.cnpq.br
Insights
Exposure to sodium valproate (VPA) during early brain development in rats temporarily impaired spatial learning and memory. These neurobehavioral deficits were not observed when testing occurred later, suggesting a transient effect.
Area of Science:
- Neuroscience
- Developmental Biology
- Pharmacology
Background:
- The brain is highly susceptible to teratogenic effects during the brain growth spurt (human third trimester).
- Anticonvulsant use in pregnancy, like sodium valproate (VPA), is linked to offspring neurodevelopmental risks, but effects during critical growth periods are unclear.
Purpose of the Study:
- To investigate the impact of VPA exposure during the early postnatal brain growth spurt on spatial learning and memory in juvenile rats.
Main Methods:
- Long-Evans rats received daily VPA (200mg/kg) or saline from postnatal day 4 to 10.
- Morris water maze tests were conducted at postnatal day 23 and postnatal day 30.
Main Results:
- VPA exposure significantly impaired swimming speed and spatial learning/memory in rats tested at postnatal day 23.
- No significant differences in performance were found between VPA-exposed and control rats tested later, from postnatal day 30 to 35.
Conclusions:
- VPA exposure during the early postnatal brain growth spurt can cause temporary neurobehavioral deficits in spatial learning and memory.
- The observed deficits appear to be transient, resolving by later developmental stages.
Abstract:
The brain is extremely vulnerable to teratogenic insults during the brain growth spurt, a period that starts during the third trimester of human gestation and is characterized by synaptogenesis establishment of neuronal circuits. While the treatment of epilepsy during pregnancy increases the risk of neurodevelopmental disorders in offspring, the consequences of exposure to anticonvulsants during the brain growth spurt remain poorly known. Here we investigate whether exposure to sodium valproate (VPA) during a similar period in rats impairs spatial learning of juvenile rats. Long-Evans rats were exposed to VPA (200mg/kg) or saline solution (SAL) every other day between postnatal day (PN) 4 and PN10. At PN23 and PN30, Morris water maze performance was evaluated during 6 consecutive days. In the group of animals which started their tests at PN23, the VPA exposure impaired both, swimming speed and learning/memory performance. Interestingly, no differences were observed between VPA and control animals tested from PN30 to PN35. Our data suggests that the neurobehavioral deficits caused by VPA exposure during the brain growth spurt are transitory.

