title: Reelin has a preventive effect on phencyclidine-induced cognitive and sensory-motor gating deficits.
abstract: Reelin has recently attracted attention because of its connection to several neuropsychiatric diseases. We previously reported the finding that prior transplantation of GABAergic neuron precursor cells into the medial prefrontal cortex (mPFC) of mice significantly prevented the induction of cognitive and sensory-motor gating deficits induced by phencyclidine (PCP). The majority of the precursor cells transplanted into the mPFC of the recipient mice differentiated into members of a somatostatin/Reelin-expressing class of GABAergic interneurons. These findings raised the possibility that Reelin secreted by the transplanted cells plays an important role in preventing the deficits induced by PCP. In this study, we investigated whether Reelin itself has a preventive effect on PCP-induced behavioral phenotypes by injecting conditioned medium containing Reelin into the lateral ventricle of the brains of 6- to 7-week-old male mice before administrating PCP. Behavioral analyses showed that the prior Reelin injection had a preventive effect against induction of the cognitive and sensory-motor gating deficits associated with PCP. Moreover, one of the types of Reelin receptor was found to be expressed by neurons in the mPFC. The results of this study point to the Reelin signaling pathway as a candidate target for the pharmacologic treatment of neuropsychiatric diseases.
authors.affiliation: Department of Anatomy, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Ishii
authors.affiliation: Department of Neuropsychopharmacology and Hospital Pharmacy, Nagoya University School of Medicine, Nagoya, Japan.
authors.forename: Taku
authors.initials: T
authors.lastname: Nagai
authors.affiliation: Department of Anatomy, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Hirota
authors.affiliation: Department of Anatomy, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Mariko
authors.initials: M
authors.lastname: Noda
authors.affiliation: Department of Regional Pharmaceutical Care & Sciences, Meijo University, Nagoya, Japan; NPO Japanese Drug Organization of Appropriate Use and Research, Nagoya, Japan.
authors.forename: Toshitaka
authors.initials: T
authors.lastname: Nabeshima
authors.affiliation: Department of Neuropsychopharmacology and Hospital Pharmacy, Nagoya University School of Medicine, Nagoya, Japan.
authors.forename: Kiyofumi
authors.initials: K
authors.lastname: Yamada
authors.affiliation: Department of Anatomy, Keio University School of Medicine, Tokyo, Japan. Electronic address: kkubo@a6.keio.jp.
authors.forename: Ken-ichiro
authors.initials: K
authors.lastname: Kubo
authors.affiliation: Department of Anatomy, Keio University School of Medicine, Tokyo, Japan. Electronic address: kazunori@keio.jp.
authors.forename: Kazunori
authors.initials: K
authors.lastname: Nakajima
mesh_terms: D000818:Animals; D015816:Cell Adhesion Molecules, Neuronal / Q000008:administration & dosage* / Q000378:metabolism*; D003072:Cognition Disorders / Q000139:chemically induced / Q000517:prevention & control*; D016326:Extracellular Matrix Proteins / Q000008:administration & dosage* / Q000378:metabolism*; D059330:GABAergic Neurons; D057967:Infusions, Intraventricular; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D009419:Nerve Tissue Proteins / Q000008:administration & dosage* / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism; D010622:Phencyclidine / Q000633:toxicity; D017397:Prefrontal Cortex / Q000378:metabolism; D011973:Receptors, LDL / Q000378:metabolism; D000091042:Reelin Protein; D055139:Sensory Gating / Q000187:drug effects*; D012697:Serine Endopeptidases / Q000008:administration & dosage* / Q000378:metabolism*
chemical_list: D015816:Cell Adhesion Molecules, Neuronal; D016326:Extracellular Matrix Proteins; D009419:Nerve Tissue Proteins; D011973:Receptors, LDL; D000091042:Reelin Protein; C036053:VLDL receptor; C000717128:Reln protein, mouse; D012697:Serine Endopeptidases; D010622:Phencyclidine
keywords: Cognitive deficits; GABAergic interneuron; Phencyclidine; Reelin; Schizophrenia; Sonsory-motor gating deficits