title: Serotonin 5-HT7 receptor increases the density of dendritic spines and facilitates synaptogenesis in forebrain neurons.
abstract: 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. Read the Editorial Highlight for this article on page 644.
authors.affiliation: Institute of Genetics and Biophysics "Adriano Buzzati Traverso", CNR, Naples, Italy.|Cellular Neurophysiology, Hannover Medical School, Hannover, Germany.|Dominick P. Purpura, Department of Neuroscience Albert Einstein College of Medicine, New York, New York, USA.
authors.forename: Luisa
authors.initials: L
authors.lastname: Speranza
authors.affiliation: Cellular Neurophysiology, Hannover Medical School, Hannover, Germany.
authors.forename: Josephine
authors.initials: J
authors.lastname: Labus
authors.affiliation: University of Naples Federico II, Naples, Italy.
authors.forename: Floriana
authors.initials: F
authors.lastname: Volpicelli
authors.affiliation: Cellular Neurophysiology, Hannover Medical School, Hannover, Germany.
authors.forename: Daria
authors.initials: D
authors.lastname: Guseva
authors.affiliation: Department of Pharmacy, University of Bari "A. Moro", Bari, Italy.
authors.forename: Enza
authors.initials: E
authors.lastname: Lacivita
authors.affiliation: Department of Pharmacy, University of Bari "A. Moro", Bari, Italy.
authors.forename: Marcello
authors.initials: M
authors.lastname: Leopoldo
authors.affiliation: Institute of Genetics and Biophysics "Adriano Buzzati Traverso", CNR, Naples, Italy.|IRCCS Neuromed, Pozzilli (IS), Italy.
authors.forename: Gian Carlo
authors.initials: GC
authors.lastname: Bellenchi
authors.affiliation: Institute of Genetics and Biophysics "Adriano Buzzati Traverso", CNR, Naples, Italy.
authors.forename: Umberto
authors.initials: U
authors.lastname: di Porzio
authors.affiliation: Cellular Neurophysiology, Hannover Medical School, Hannover, Germany.|Department of Molecular and Cellular Neurobiology, Nencki Institute, Warsaw, Poland.
authors.forename: Monika
authors.initials: M
authors.lastname: Bijata
authors.affiliation: Institute of Genetics and Biophysics "Adriano Buzzati Traverso", CNR, Naples, Italy.|University of Naples Federico II, Naples, Italy.
authors.forename: Carla
authors.initials: C
authors.lastname: Perrone-Capano
authors.affiliation: Cellular Neurophysiology, Hannover Medical School, Hannover, Germany.
authors.forename: Evgeni
authors.initials: E
authors.lastname: Ponimaskin
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology*; D003342:Corpus Striatum / Q000166:cytology*; D049229:Dendritic Spines / Q000187:drug effects / Q000378:metabolism*; D004224:Diterpenes; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009415:Nerve Net / Q000187:drug effects / Q000502:physiology; D055495:Neurogenesis / Q000187:drug effects / Q000235:genetics*; D009474:Neurons / Q000166:cytology* / Q000187:drug effects; D010879:Piperazines / Q000494:pharmacology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011985:Receptors, Serotonin / Q000235:genetics / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D013569:Synapses / Q000187:drug effects / Q000235:genetics*; D013997:Time Factors
chemical_list: D019086:Bridged Bicyclo Compounds, Heterocyclic; D004224:Diterpenes; C573815:N-(4-cyanophenylmethyl)-4-(2-diphenyl)-1-piperazinehexanamide; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; C104425:serotonin 7 receptor; C508887:retapamulin
keywords: 5-HT7R; Cdc42; Cdk5; dendritic spines; neurite outgrowth; synaptogenesis