Prenatal Exposure to Histone Deacetylase Inhibitors Affects Gene Expression of Autism-Related Molecules and Delays Neuronal Maturation
| Autor: | Takuya Kawanai, Hitoshi Hashimoto, Shigeru Hasebe, Toshio Matsuda, Aya Inoue, Atsuki Taruta, Yusuke Onaka, Yukio Ago, Kazuhiro Takuma, Ryo Watanabe |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Offspring Neurogenesis Biochemistry Histone Deacetylases Andrology Histones 03 medical and health sciences Cellular and Molecular Neuroscience Mice 0302 clinical medicine Pregnancy Gene expression medicine Animals Autistic Disorder Neurons Valproic Acid biology Gene Expression Regulation Developmental Embryo General Medicine Transfection Molecular biology Histone Deacetylase Inhibitors 030104 developmental biology Histone Trichostatin A Prenatal Exposure Delayed Effects embryonic structures biology.protein Female Histone deacetylase 030217 neurology & neurosurgery medicine.drug |
| Zdroj: | Neurochemical research. 41(10) |
| ISSN: | 1573-6903 |
| Popis: | Valproic acid (VPA) is a multi-target drug and an inhibitor of histone deacetylase (HDAC). We have previously demonstrated that prenatal exposure to VPA at embryonic day 12.5 (E12.5), but not at E14.5, causes autism-like behavioral abnormalities in male mouse offspring. We have also found that prenatal VPA exposure causes transient histone hyperacetylation in the embryonic brain, followed by decreased neuronal cell numbers in the prefrontal and somatosensory cortices after birth. In the present study, we examined whether prenatal HDAC inhibition affects neuronal maturation in primary mouse cortical neurons. Pregnant mice were injected intraperitoneally with VPA (500 mg/kg) and the more selective HDAC inhibitor trichostatin A (TSA; 500 µg/kg) at E12.5 or E14.5, and primary neuronal cultures were prepared from the cerebral cortices of their embryos. Prenatal exposure to VPA at E12.5, but not at E14.5, decreased total number, total length, and complexity of neuronal dendrites at 14 days in vitro (DIV). The effects of VPA weakened at 21 DIV. Exposure to TSA at E12.5, but not at E14.5, also delayed maturation of cortical neurons. In addition, real-time quantitative PCR revealed that the prenatal exposure to TSA decreased neuroligin-1 (Nlgn1), Shank2, and Shank3 mRNA levels and increased contactin-associated protein-like 2 mRNA level. The delay in neuronal maturation was also observed in Nlgn1-knockdown cells, which were transfected with Nlgn1 siRNA. These findings suggest that prenatal HDAC inhibition causes changes in gene expression of autism-related molecules linked to a delay of neuronal maturation. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full text from SpringerLink