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The long‐term prognosis of hippocampal neurogenesis and behavioral changes of offspring from rats exposed to valproic acid during pregnancy
AIM: In pregnant women with epilepsy, it is essential to balance maternal safety and the potential teratogenicity of anticonvulsants. Recently, growing evidence has indicated that valproic acid (VPA) can produce postnatal congenital malformations and impair cognitive function. However, the mechanism...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8340817/ https://www.ncbi.nlm.nih.gov/pubmed/33949804 http://dx.doi.org/10.1002/npr2.12181 |
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author | Ito, Masanobu Kinjo, Tomoya Seki, Tatsunori Horie, Junko Suzuki, Toshihito |
author_facet | Ito, Masanobu Kinjo, Tomoya Seki, Tatsunori Horie, Junko Suzuki, Toshihito |
author_sort | Ito, Masanobu |
collection | PubMed |
description | AIM: In pregnant women with epilepsy, it is essential to balance maternal safety and the potential teratogenicity of anticonvulsants. Recently, growing evidence has indicated that valproic acid (VPA) can produce postnatal congenital malformations and impair cognitive function. However, the mechanisms underlying cognitive dysfunction in long‐term prognoses remain unclear. METHODS: Pregnant Wistar rats received daily intraperitoneal injections of VPA (200 mg/kg/day) from embryonic day 12.5 until birth. On postnatal day (PD) 149, the rats received an injection of bromodeoxyuridine (BrdU). On PD 150, the rats were subjected to the open field (OF), elevated plus‐maze (EPM), and Y‐maze tests. After behavioral testing, perfusion fixation was performed and the brain was dissected for immunohistochemistry. RESULTS: A significant marked decrease was seen in the number of BrdU‐positive cells in the dentate gyrus of offspring of VPA‐treated dams compared to those of control. However, no significant differences in hyperactivity were found based on the results of the OF test among the offspring on PD 150 of 200 VPA‐treated dams. In addition, no significant differences were seen in the EPM test. CONCLUSION: The behavioral abnormality observed in young offspring of VPA‐treated dams was not significantly different from that of controls in adult offspring on PD 150. However, compared with controls, the number of BrdU‐positive cells in VPA‐treated rats was halved. The findings suggest that the behavioral abnormality seems to improve as they grow, even if some structural abnormalities may remain in the central nervous system. |
format | Online Article Text |
id | pubmed-8340817 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-83408172021-08-11 The long‐term prognosis of hippocampal neurogenesis and behavioral changes of offspring from rats exposed to valproic acid during pregnancy Ito, Masanobu Kinjo, Tomoya Seki, Tatsunori Horie, Junko Suzuki, Toshihito Neuropsychopharmacol Rep Micro Reports AIM: In pregnant women with epilepsy, it is essential to balance maternal safety and the potential teratogenicity of anticonvulsants. Recently, growing evidence has indicated that valproic acid (VPA) can produce postnatal congenital malformations and impair cognitive function. However, the mechanisms underlying cognitive dysfunction in long‐term prognoses remain unclear. METHODS: Pregnant Wistar rats received daily intraperitoneal injections of VPA (200 mg/kg/day) from embryonic day 12.5 until birth. On postnatal day (PD) 149, the rats received an injection of bromodeoxyuridine (BrdU). On PD 150, the rats were subjected to the open field (OF), elevated plus‐maze (EPM), and Y‐maze tests. After behavioral testing, perfusion fixation was performed and the brain was dissected for immunohistochemistry. RESULTS: A significant marked decrease was seen in the number of BrdU‐positive cells in the dentate gyrus of offspring of VPA‐treated dams compared to those of control. However, no significant differences in hyperactivity were found based on the results of the OF test among the offspring on PD 150 of 200 VPA‐treated dams. In addition, no significant differences were seen in the EPM test. CONCLUSION: The behavioral abnormality observed in young offspring of VPA‐treated dams was not significantly different from that of controls in adult offspring on PD 150. However, compared with controls, the number of BrdU‐positive cells in VPA‐treated rats was halved. The findings suggest that the behavioral abnormality seems to improve as they grow, even if some structural abnormalities may remain in the central nervous system. John Wiley and Sons Inc. 2021-05-05 /pmc/articles/PMC8340817/ /pubmed/33949804 http://dx.doi.org/10.1002/npr2.12181 Text en © 2021 The Authors. Neuropsychopharmacology Reports published by John Wiley & Sons Australia, Ltd on behalf of the Japanese Society of Neuropsychopharmacology https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made. |
spellingShingle | Micro Reports Ito, Masanobu Kinjo, Tomoya Seki, Tatsunori Horie, Junko Suzuki, Toshihito The long‐term prognosis of hippocampal neurogenesis and behavioral changes of offspring from rats exposed to valproic acid during pregnancy |
title | The long‐term prognosis of hippocampal neurogenesis and behavioral changes of offspring from rats exposed to valproic acid during pregnancy |
title_full | The long‐term prognosis of hippocampal neurogenesis and behavioral changes of offspring from rats exposed to valproic acid during pregnancy |
title_fullStr | The long‐term prognosis of hippocampal neurogenesis and behavioral changes of offspring from rats exposed to valproic acid during pregnancy |
title_full_unstemmed | The long‐term prognosis of hippocampal neurogenesis and behavioral changes of offspring from rats exposed to valproic acid during pregnancy |
title_short | The long‐term prognosis of hippocampal neurogenesis and behavioral changes of offspring from rats exposed to valproic acid during pregnancy |
title_sort | long‐term prognosis of hippocampal neurogenesis and behavioral changes of offspring from rats exposed to valproic acid during pregnancy |
topic | Micro Reports |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8340817/ https://www.ncbi.nlm.nih.gov/pubmed/33949804 http://dx.doi.org/10.1002/npr2.12181 |
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