Involvement of 5-HT1A receptor-mediated histone acetylation in the regulation of depression. 2021

Li-Juan Zhu, and Yan-Qiu Sun, and Shuang Wang, and Hu-Jiang Shi, and Na Li
Key Laboratory of Developmental Genes and Human Diseases, MOE, Department of Histology and Embryology, School of Medicine, Southeast University, Nanjing, Jiangsu, 210009, PR China.

Depression is one of the most common and disabling mental disorders. There is growing evidence that 5-HT1A receptor is involved in the regulation of depressive-related behaviors. However, the exact mechanism underlying the role of 5-HT1A receptor in depression remains unknown. Histone acetylation is associated with the pathophysiology and treatment of depression. In the current study, we investigated whether the epigenetic histone deacetylase (HDAC)-induced histone acetylation mediates the regulation of 5-HT1A receptor in depressive behaviors. We showed that 5-HT1A receptor selective agonist (±)-8-hydroxy-2-(dipropylamino) tetralin hydrobromide led to significant increase in acetylation of H3 at lysine 9 (Ac-H3K9) and H4 at lysine 5 (Ac-H4K5) and lysine 12 (Ac-H4K12) with obviously decreasing histone deacetylase 1 (HDAC1), histone deacetylase 2 (HDAC2), histone deacetylase 4 (HDAC4) and histone deacetylase 5 (HDAC5) expression in hippocampus of mice. Conversely, 5-HT1A receptor selective antagonist NAN-190 decreased the level of acetylation of H3 and H4 with increasing the expression of HDAC1, HDAC2, HDAC4 and HDAC5 in the hippocampus. Furthermore, we found that HDAC inhibitors, trichostatin A or suberoylanilide hydroxamic acid infusion to hippocampus prevented the depressive behaviors induced by NAN-190, as well as histone H3 and H4 acetylation in mice. Our results suggested that epigenetic histone acetylation coupled with 5-HT1A receptor may play vital role in the pathophysiology and treatment of depressive disorders.

UI MeSH Term Description Entries
D008297 Male Males
D008810 Mice, Inbred C57BL One of the first INBRED MOUSE STRAINS to be sequenced. This strain is commonly used as genetic background for transgenic mouse models. Refractory to many tumors, this strain is also preferred model for studying role of genetic variations in development of diseases. Mice, C57BL,Mouse, C57BL,Mouse, Inbred C57BL,C57BL Mice,C57BL Mice, Inbred,C57BL Mouse,C57BL Mouse, Inbred,Inbred C57BL Mice,Inbred C57BL Mouse
D003863 Depression Depressive states usually of moderate intensity in contrast with MAJOR DEPRESSIVE DISORDER present in neurotic and psychotic disorders. Depressive Symptoms,Emotional Depression,Depression, Emotional,Depressive Symptom,Symptom, Depressive
D006624 Hippocampus A curved elevation of GRAY MATTER extending the entire length of the floor of the TEMPORAL HORN of the LATERAL VENTRICLE (see also TEMPORAL LOBE). The hippocampus proper, subiculum, and DENTATE GYRUS constitute the hippocampal formation. Sometimes authors include the ENTORHINAL CORTEX in the hippocampal formation. Ammon Horn,Cornu Ammonis,Hippocampal Formation,Subiculum,Ammon's Horn,Hippocampus Proper,Ammons Horn,Formation, Hippocampal,Formations, Hippocampal,Hippocampal Formations,Hippocampus Propers,Horn, Ammon,Horn, Ammon's,Proper, Hippocampus,Propers, Hippocampus,Subiculums
D006655 Histone Deacetylases Deacetylases that remove N-acetyl groups from amino side chains of the amino acids of HISTONES. The enzyme family can be divided into at least three structurally-defined subclasses. Class I and class II deacetylases utilize a zinc-dependent mechanism. The sirtuin histone deacetylases belong to class III and are NAD-dependent enzymes. Class I Histone Deacetylases,Class II Histone Deacetylases,HDAC Proteins,Histone Deacetylase,Histone Deacetylase Complexes,Complexes, Histone Deacetylase,Deacetylase Complexes, Histone,Deacetylase, Histone,Deacetylases, Histone
D000107 Acetylation Formation of an acetyl derivative. (Stedman, 25th ed) Acetylations
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D017366 Serotonin Receptor Agonists Endogenous compounds and drugs that bind to and activate SEROTONIN RECEPTORS. Many serotonin receptor agonists are used as ANTIDEPRESSANTS; ANXIOLYTICS; and in the treatment of MIGRAINE DISORDERS. 5-HT Agonists,5-Hydroxytryptamine Agonists,Serotonin Agonists,5-HT Agonist,5-Hydroxytrytamine Agonist,Receptor Agonists, Serotonin,Serotonergic Agonist,Serotonergic Agonists,Serotonin Agonist,Serotonin Receptor Agonist,5 HT Agonist,5 HT Agonists,5 Hydroxytryptamine Agonists,5 Hydroxytrytamine Agonist,Agonist, 5-HT,Agonist, 5-Hydroxytrytamine,Agonist, Serotonergic,Agonist, Serotonin,Agonist, Serotonin Receptor,Agonists, 5-HT,Agonists, 5-Hydroxytryptamine,Agonists, Serotonergic,Agonists, Serotonin,Agonists, Serotonin Receptor,Receptor Agonist, Serotonin
D017371 8-Hydroxy-2-(di-n-propylamino)tetralin A serotonin 1A-receptor agonist that is used experimentally to test the effects of serotonin. 8-OH-DPAT,8-Hydroxy-2-(di-n-propylamino)tetralin Hydrobromide,8-Hydroxy-2-(di-n-propylamino)tetralin Hydrobromide, (+-)-Isomer,8-Hydroxy-2-(di-n-propylamino)tetralin Hydrobromide, (R)-Isomer,,8-Hydroxy-2-(di-n-propylamino)tetralin Hydrobromide, (S)-Isomer,,8-Hydroxy-2-(di-n-propylamino)tetralin Hydrochloride, (R)-Isomer,,8-Hydroxy-2-(di-n-propylamino)tetralin Hydrochloride, (S)-Isomer,8-Hydroxy-2-(di-n-propylamino)tetralin, (+-)-Isomer,8-Hydroxy-2-(di-n-propylamino)tetralin, (R)-Isomer,8-Hydroxy-2-(di-n-propylamino)tetralin, (S)-Isomer
D044282 Receptor, Serotonin, 5-HT1A A serotonin receptor subtype found distributed through the CENTRAL NERVOUS SYSTEM where they are involved in neuroendocrine regulation of ACTH secretion. The fact that this serotonin receptor subtype is particularly sensitive to SEROTONIN RECEPTOR AGONISTS such as BUSPIRONE suggests its role in the modulation of ANXIETY and DEPRESSION. Serotonin 1A Receptor,5-HT(1A) Receptor,5-HT1A Receptor,5-Hydroxytryptamine 1A Receptor,5-Hydroxytryptamine 1A Receptors,Receptor, 5-Hydroxytryptamine 1A,Serotonin Receptor, 5-HT1A,Serotonin, 5-HT1a Receptor,1A Receptor, 5-Hydroxytryptamine,1A Receptors, 5-Hydroxytryptamine,5 HT1A Receptor,5 Hydroxytryptamine 1A Receptor,5 Hydroxytryptamine 1A Receptors,5-HT1A Serotonin Receptor,5-HT1a Receptor Serotonin,Receptor Serotonin, 5-HT1a,Receptor, 5 Hydroxytryptamine 1A,Receptor, 5-HT1A,Receptor, 5-HT1A Serotonin,Receptor, Serotonin 1A,Receptors, 5-Hydroxytryptamine 1A,Serotonin Receptor, 5 HT1A,Serotonin, 5 HT1a Receptor

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