지원사업
학술연구/단체지원/교육 등 연구자 활동을 지속하도록 DBpia가 지원하고 있어요.
커뮤니티
연구자들이 자신의 연구와 전문성을 널리 알리고, 새로운 협력의 기회를 만들 수 있는 네트워킹 공간이에요.
논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 발행연도
- 2014.1
- 수록면
- 406 - 413 (8page)
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초록· 키워드
오류제보하기
to valproic acid (VPA) during pregnancy produces ASD-like core behavioral phenotypes as well as hyperactivity in offspring both in human and experimental animals, which makes it a plausible model to study ASD-related neurobiological processes. In this study, we examined the effects of two of currently available attention defecit hyperactivity disorder (ADHD) medications, methylphenidate (MPH) and atomoxetine (ATX) targeting dopamine and norepinephrine transporters (DAT and NET), respectively, on hyperactive behavior of prenatally VPA-exposed rat offspring. In the prefrontal cortex of VPA exposed rat offspring, both mRNA and protein expression of DAT was increased as compared with control. VPA function as a histone deacetylase inhibitor (HDACi) and chromatin immunoprecipitation experiments demonstrated that the acetylation of histone bound to DAT gene promoter was increased in VPA-exposed rat offspring suggesting epigenetic mechanism of DAT regulation. Similarly, the expression of NET was increased, possibly via increased histone acetylation in prefrontal cortex of VPA-exposed rat offspring. When we treated the VPA-exposed rat offspring with ATX, a NET selective inhibitor, hyperactivity was reversed to control level. In contrast, MPH that inhibits both DAT and NET, did not produce inhibitory effects against hyperactivity. The results suggest that NET abnormalities may underlie the hyperactive phenotype in VPA animal model of ASD. Profiling the pharmacological responsiveness as well as investigating underlying mechanism in multiple models of ASD and ADHD may provide more insights into the neurobiological correlates regulating the behavioral abnormalities.
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참고문헌 (50)
참고문헌 신청
Ali, E. H / 2013 / Combined prenatal and postnatalbutyl paraben exposure produces autism-like symptoms in offspring:Comparison with valproic acid autistic model / Pharmacol.Biochem. Behav 111:102~110
Baf, M. H / 1994 / Sodium valproate induced alterations in monoamine levels in differentregions of the rat brain / Neurochem. Int 24:67~72
Banerjee, S / 2014 / Genetic aspects of autismspectrum disorders: insights from animal models / Front. Cell.Neurosci 8:58
Barr, A. M / 2004 / The selective serotonin-2Areceptor antagonist M100907 reverses behavioral deficits in dopaminetransporter knockout mice / Neuropsychopharmacology 29:221~228
Barr, C. L / 2001 / Attention-deficit hyperactivitydisorder and the adrenergic receptors alpha 1C and alpha 2C / Mol. Psychiatry 6:334~337
Baf, M. H / 1994 / Sodium valproate induced alterations in monoamine levels in differentregions of the rat brain / Neurochem. Int 24:67~72
Banerjee, S / 2014 / Genetic aspects of autismspectrum disorders: insights from animal models / Front. Cell.Neurosci 8:58
Barr, A. M / 2004 / The selective serotonin-2Areceptor antagonist M100907 reverses behavioral deficits in dopaminetransporter knockout mice / Neuropsychopharmacology 29:221~228
Barr, C. L / 2001 / Attention-deficit hyperactivitydisorder and the adrenergic receptors alpha 1C and alpha 2C / Mol. Psychiatry 6:334~337
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