title: Survival of corticostriatal neurons by Rho/Rho-kinase signaling pathway.
abstract: Developing cortical neurons undergo a number of sequential developmental events including neuronal survival/apoptosis, and the molecular mechanism underlying each characteristic process has been studied in detail. However, the survival pathway of cortical neurons at mature stages remains largely uninvestigated. We herein focused on mature corticostriatal neurons because of their important roles in various higher brain functions and the spectrum of neurological and neuropsychiatric disorders. The small GTPase Rho is known to control diverse and essential cellular functions through some effector molecules, including Rho-kinase, during neural development. In the present study, we investigated the role of Rho signaling through Rho-kinase in the survival of corticostriatal neurons. We performed the conditional expression of Clostridium botulinum C3 ADP-ribosyltransferase (C3 transferase) or dominant-negative form for Rho-kinase (Rho-K DN), a well-known inhibitor of Rho or Rho-kinase, respectively, in corticostriatal neurons using a dual viral vector approach combining a neuron-specific retrograde gene transfer lentiviral vector and an adeno-associated virus vector. C3 transferase markedly decreased the number of corticostriatal neurons, which was attributed to caspase-3-dependent enhanced apoptosis. In addition, Rho-K DN produced phenotypic defects similar to those caused by C3 transferase. These results indicate that the Rho/Rho-kinase signaling pathway plays a crucial role in the survival of corticostriatal neurons.
authors.affiliation: Section of Viral Vector Development, National Institute for Physiological Sciences, Okazaki 444-8585, Japan; SOKENDAI (The Graduate University for Advanced Studies), Hayama 240-0193, Japan. Electronic address: kobaya@nips.ac.jp.
authors.forename: Kenta
authors.initials: K
authors.lastname: Kobayashi
authors.affiliation: SOKENDAI (The Graduate University for Advanced Studies), Hayama 240-0193, Japan; Division of System Neurophysiology, National Institute for Physiological Sciences, Okazaki 444-8585, Japan.
authors.forename: Hiromi
authors.initials: H
authors.lastname: Sano
authors.affiliation: Department of Molecular Genetics, Institute of Biomedical Sciences, Fukushima Medical University School of Medicine, Fukushima 960-1295, Japan.
authors.forename: Shigeki
authors.initials: S
authors.lastname: Kato
authors.affiliation: Department of Cell Pharmacology, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Kuroda
authors.affiliation: Department of Cell Pharmacology, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan.
authors.forename: Shinichi
authors.initials: S
authors.lastname: Nakamuta
authors.affiliation: Section of Viral Vector Development, National Institute for Physiological Sciences, Okazaki 444-8585, Japan; SOKENDAI (The Graduate University for Advanced Studies), Hayama 240-0193, Japan; Department of Developmental Physiology, National Institute for Physiological Sciences, Okazaki 444-8585, Japan.
authors.forename: Tadashi
authors.initials: T
authors.lastname: Isa
authors.affiliation: Section of Viral Vector Development, National Institute for Physiological Sciences, Okazaki 444-8585, Japan; SOKENDAI (The Graduate University for Advanced Studies), Hayama 240-0193, Japan; Division of System Neurophysiology, National Institute for Physiological Sciences, Okazaki 444-8585, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Nambu
authors.affiliation: Department of Cell Pharmacology, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan.
authors.forename: Kozo
authors.initials: K
authors.lastname: Kaibuchi
authors.affiliation: Department of Molecular Genetics, Institute of Biomedical Sciences, Fukushima Medical University School of Medicine, Fukushima 960-1295, Japan.
authors.forename: Kazuto
authors.initials: K
authors.lastname: Kobayashi
mesh_terms: D036002:ADP Ribose Transferases / Q000235:genetics / Q000378:metabolism; D000818:Animals; D017209:Apoptosis; D001905:Botulinum Toxins / Q000235:genetics / Q000378:metabolism; D002470:Cell Survival; D002540:Cerebral Cortex / Q000378:metabolism*; D003342:Corpus Striatum / Q000378:metabolism*; D000229:Dependovirus / Q000502:physiology; D005822:Genetic Vectors / Q000008:administration & dosage; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009434:Neural Pathways / Q000378:metabolism; D009474:Neurons / Q000378:metabolism*; D015398:Signal Transduction; D013003:Somatosensory Cortex / Q000378:metabolism; D054460:rho-Associated Kinases / Q000378:metabolism*
chemical_list: D036002:ADP Ribose Transferases; C063007:exoenzyme C3, Clostridium botulinum; D054460:rho-Associated Kinases; D001905:Botulinum Toxins
keywords: Corticostriatal neuron; Neuronal survival; Rho GTPase; Rho-kinase; Viral vector