期刊文献+

表观遗传对老年人群抗精神病药疗效的调节:组蛋白脱乙酰基酶抑制剂的临床前研究(英文)

Epigenetic regulation on antipsychotic efficacy in the elderly population:preclinical aspects of histone deacetylase inhibitors
下载PDF
导出
摘要 抗精神病药已被广泛地用于治疗老年人的精神性严重疾病,包括精神分裂症和伴有认知功能受损的行为障碍。这种用药不仅未达到预期的治疗效果,相反,还给老年人带来了一系列的不良反应。但涉及的机制目前仍不清楚,而年龄相关的表观遗传改变可能是其机制之一。本综述主要介绍与年龄相关的表观遗传改变及其对老年人使用抗精神病药效果的影响。重点讨论动物模型中组蛋白脱乙酰基酶抑制剂(HDAci)改变老年表观遗传从而增强抗精神病药的潜在的表观遗传改变。了解对药物疗效表观遗传效应的作用机制,有助于在使用抗精神病药的老年人群中发现增强药效降低不良反应的新策略。 Antipsychotic drugs are widely prescribed to elderly patients for the treatment of a variety of psycho-pathological conditions including psychosis and behavioral disturbances associated with cognitive impairment.However,the outcomes of treatments are not as effective as expected and the severity of side effects is prominent in the elderly.While the mechanisms are not well understood,the age-related epigenetic alterations may be the one of the mechanisms.The aim of this review is to introduce the epigenetic alterations with aging and its impacts on the antipsychotic drug efficacy in this population.In particular,this review discusses the potential epigenetic correction by treatment of histone deacetylase inhibitors(HDACis) to increase antipsychotic drugs efficacy in animal models.Understanding the mechanisms underlying epigenetic effects on drug efficacy will help develop new strategies to increase benefits and decrease side effects of psychotropic medications in the elderly population.
出处 《遵义医学院学报》 2014年第3期255-262,共8页 Journal of Zunyi Medical University
关键词 抗精神病药 老年人群 表观遗传效应 组蛋白脱乙酰基酶抑制剂 antipsychotic drugs elderly population epigenetic effects histone deacetylase inhibitors
  • 相关文献

参考文献75

  • 1Hien le T T,Cumming R G,Cameron I D,et al.Atypical antipsychotic medications and risk of falls in residents of aged care facilities[J].J Am Geriatr Soc,2005,53(8):1290-1295.
  • 2Schneider L S,Dagerman K S,Insel P.Risk of death with atypical antipsychotic drug treatment for dementia:meta-analysis of randomized placebo-controlled trials[J].Jama,2005,294(15):1934-1943.
  • 3Uchida H,Mamo D C,Mulsant H,et al.Increased antipsychotic sensitivity in elderly patients:evidence and mechanisms[J].J Clin Psychiatry,2009,70(3):397-405.
  • 4Pinner G,Bouman W P.To tell or not to tell:on disclosing the diagnosis of dementia[J].Int Psychogeriatr,2002,14(2):127-137.
  • 5Mitchell C,Blaho J A,Roizman B.Casein kinase Ⅱ specifically nucleotidylylates in vitro the amino acid sequence of the protein encoded by the alpha 22 gene of herpes simplex virus 1[J].Proc Natl Acad Sci USA,1994,91(25):11864-11868.
  • 6Avorn J,Monane M,Everitt D E,et al.Clinical assessment of extrapyramidal signs in nursing home patients given antipsychotic medication[J].Arch Intern Med,1994,154(10):1113-1117.
  • 7Deng C.Effects of antipsychotic medications on appetite,weight,and insulin resistance[J].Endocrinology and metabolism clinics of North America,2013,42 (3):545-563.
  • 8Valjent E,Bertran-Gonzalez J,Bowling H,et al.Haloperidol regulates the state of phosphorylation of ribosomal protein S6 via activation of PKA and phosphorylation of DARPP-32[J].Neuropsychopharmacology,2011,36(12):2561-2570.
  • 9Robertson G S,Matsumura H,Fibiger H C.Induction patterns of Fos-like immunoreactivity in the forebrain as predictors of atypical antipsychotic activity[J].J Pharmacol Exp Ther,1994,271 (2):1058-1066.
  • 10Hiroi N,Graybiel A M.Atypical and typical neuroleptic treatments induce distinct programs of transcription factor expression in the striatum[J].J Comp Neurol,1996,374(1):70-83.

相关作者

内容加载中请稍等...

相关机构

内容加载中请稍等...

相关主题

内容加载中请稍等...

浏览历史

内容加载中请稍等...
;
使用帮助 返回顶部