Journal
JOURNAL OF NEUROCHEMISTRY
Volume 141, Issue 5, Pages 647-661Publisher
WILEY
DOI: 10.1111/jnc.13962
Keywords
5-HT7R; Cdc42; Cdk5; dendritic spines; neurite outgrowth; synaptogenesis
Categories
Funding
- DFG [Po732]
- DFG Excellence Cluster Rebirth
- Finanziamento Ricerca di Ateneo
- Polish Ministry of Science [1342/1/MOB/IV/15/2016/0]
- GLISTEN-COST action
- FEBS
- [FIRB-RBIN062YH4]
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Precise control of dendritic spine density and synapse formation is critical for normal and pathological brain functions. Therefore, signaling pathways influencing dendrite outgrowth and remodeling remain a subject of extensive investigations. Here, we report that prolonged activation of the serotonin 5-HT7 receptor (5-HT7R) with selective agonist LP-211 promotes formation of dendritic spines and facilitates synaptogenesis in postnatal cortical and striatal neurons. Critical role of 5-HT7R in neuronal morphogenesis was confirmed by analysis of neurons isolated from 5-HT7R-deficient mice and by pharmacological inactivation of the receptor. Acute activation of 5-HT7R results in pronounced neurite elongation in postnatal striatal and cortical neurons, thus extending previous data on the morphogenic role of 5-HT7R in embryonic and hippocampal neurons. We also observed decreased number of spines in neurons with either genetically (i.e. 5-HT7R-knock-out) or pharmacologically (i.e. antagonist treatment) blocked 5-HT7R, suggesting that constitutive 5-HT7R activity is critically involved in the spinogenesis. Moreover, cyclin-dependent kinase 5 and small GTPase Cdc42 were identified as important downstream effectors mediating morphogenic effects of 5-HT7R in neurons. Altogether, our data suggest that the 5-HT7R-mediated structural reorganization during the postnatal development might have a crucial role for the development and plasticity of forebrain areas such as cortex and striatum, and thereby can be implicated in regulation of the higher cognitive functions.
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