Selective reduction of drebrin and actin in dendritic spines of hippocampal neurons by activation of 5-HT_2A receptors

详细信息    查看全文

• 作者：Reiko T. Roppongi ; Nobuhiko Kojima ; Kenji Hanamura ; Hiroyuki Yamazaki ; Tomoaki Shirao ; ^{tshirao@med.gunma-u.ac.jp} ; ^{tshirao@gunma-u.ac.jp}
• 关键词：Dendritic spine ; Actin ; 5-HT2A receptor ; Hippocampal neurons ; Drebrin ; PSD-95
• 刊名：Neuroscience Letters
• 出版年：2013
• 出版时间：28 June, 2013
• 年：2013
• 卷：547
• 期：Complete
• 页码：76-81
• 全文大小：1577 K

文摘

Abnormal architecture of dendritic spines is associated with neurodevelopmental and neurodegenerative diseases. The 5-HT_2A receptor is a potential therapeutic target for mental illnesses and it is functionally and genetically associated with many types of psychiatric disorders. It has been reported that 5-HT_2A receptor activation alters spine architecture. Although actin cytoskeleton has a key role in the regulation of spine architecture, it is not clarified whether 5-HT_2A receptor activation affect the actin cytoskeleton in dendritic spines. In the present study, we examined the effect of 5-HT_2A receptor activation on the actin cytoskeleton in dendritic spines of mature hippocampal neurons in low-density culture. Immunocytochemical analysis showed that 15 min exposure of 5-HT_2A receptor agonist (¡À)-2,5-dimethoxy-4-iodoamphetamine hydrochloride (DOI) significantly decreased the cluster densities of drebrin (control, 37.0 ¡À 6.9 per 100 ¦Ìm, DOI, 12.5 ¡À 2.9) and F-actin (control, 18.3 ¡À 4.9; DOI, 7.7 ¡À 2.1) at dendritic spines without any detectable changes in the cluster densities of synapsin I and PSD-95. At the same time period DOI exposure did not affect spine architecture (spine density: control, 38.3 ¡À 5.1 per 100 ¦Ìm; DOI, 25.6 ¡À 3.5; spine length: control, 1.99 ¡À 0.18; DOI, 2.00 ¡À 0.29; spine width: control, 0.72 ¡À 0.06; DOI, 0.77 ¡À 0.11). Thus, it is indicated that decrease of drebrin and F-actin can occur at the dendritic spines without morphological changes. Together our data suggest that 5-HT_2A receptors activation is involved in the regulation of distribution of cytoskeleton in the dendritic spines.