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Antidepressant effect and mechanism of TMP269 on stress-induced depressive-like behavior in mice.
Meng, Yuan; Xiao, Lifei; Liu, Ruyun; Du, Juan; Liu, Ning; Yu, Jianqiang; Li, Yanqin; Lu, Guangyuan.
Afiliación
  • Meng Y; Key Laboratory of Cerebrocranial Disease, Incubation Base of National Key Laboratory, Ningxia Medical University, Yinchuan 750000, China; Department of Pharmacology, College of Pharmacy, Wuhan University, Wuhan 430072, China; Department of Pharmacology, College of Pharmacy, Ningxia Medical Universit
  • Xiao L; Department of Anesthesiology, Shenzhen Second People's Hospital, The First Affiliated Hospital of Shenzhen University, Shenzhen 518035, China.
  • Liu R; Key Laboratory of Cerebrocranial Disease, Incubation Base of National Key Laboratory, Ningxia Medical University, Yinchuan 750000, China; Department of Pharmacology, College of Pharmacy, Ningxia Medical University, Yinchuan 750000, China.
  • Du J; Department of Pharmacology, College of Pharmacy, Ningxia Medical University, Yinchuan 750000, China.
  • Liu N; Department of Pharmacology, College of Pharmacy, Ningxia Medical University, Yinchuan 750000, China.
  • Yu J; Department of Pharmacology, College of Pharmacy, Ningxia Medical University, Yinchuan 750000, China.
  • Li Y; Department of Pharmacology, College of Pharmacy, Wuhan University, Wuhan 430072, China. Electronic address: yqli@whu.edu.cn.
  • Lu G; Key Laboratory of Cerebrocranial Disease, Incubation Base of National Key Laboratory, Ningxia Medical University, Yinchuan 750000, China; Key Laboratory of Drug Creation and Generic Drug Research, Ningxia Medical University, Yinchuan 750000, China. Electronic address: gylulifescience@163.com.
Biochem Pharmacol ; 225: 116320, 2024 07.
Article en En | MEDLINE | ID: mdl-38801927
ABSTRACT
TMP269, a class IIA histone deacetylase inhibitor with selectivity, that has a protective effect on the central nervous system, yet its specific mechanism of action remains ambiguous. Although major depressive disorder (MDD) is highly prevalent, its pathophysiology is poorly understood. Recent evidence suggests that histone deacetylase 5 plays a key role in the pathological process of depression and the fact that preclinical studies have shown HDAC5 to be a potential antidepressant target, the search for natural drugs or small molecule compounds that can target HDAC5 may be a potential therapeutic strategy for the treatment of depression. In addition, we examined the role of the Brain-derived neurotrophic factor (BDNF), an important neurotrophic factor for neuronal survival and growth, as a potential downstream target of HDAC5. We found downward revision of HDAC5 levels in the hippocampus ameliorated depressive-like behavior in LH (Learned helplessness) mice. Furthermore, injection of HDAC5 overexpressing adenoviral vectors in the hippocampal dentate gyrus of wild-type mice produced a somewhat depressive-like phenotype. Pharmacological, immunofluorescence and biochemical experiments showed that TMP269 could produce antidepressant effects by inhibiting mouse hippocampal HDAC5 and thus modulating its downstream BDNF. Over all, TMP269 mitigated LH-induced depressive-like behaviors and abnormalities in synapse formation and neurogenesis within the hippocampus. These findings suggest potential beneficial effects of TMP269 on depression.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Estrés Psicológico / Depresión / Ratones Endogámicos C57BL / Antidepresivos Límite: Animals Idioma: En Revista: Biochem Pharmacol Año: 2024 Tipo del documento: Article Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Estrés Psicológico / Depresión / Ratones Endogámicos C57BL / Antidepresivos Límite: Animals Idioma: En Revista: Biochem Pharmacol Año: 2024 Tipo del documento: Article Pais de publicación: Reino Unido