title: Relationships among parvalbumin-immunoreactive neuron density, phase-locked gamma oscillations, and autistic/schizophrenic symptoms in PDGFR-β knock-out and control mice.
abstract: Cognitive deficits and negative symptoms are important therapeutic targets for schizophrenia and autism disorders. Although reduction of phase-locked gamma oscillation has been suggested to be a result of reduced parvalbumin-immunoreactive (putatively, GABAergic) neurons, no direct correlations between these have been established in these disorders. In the present study, we investigated such relationships during pharmacological treatment with a newly synthesized drug, T-817MA, which displays neuroprotective and neurotrophic effects. In this study, we used platelet-derived growth factor receptor-β gene knockout (PDGFR-β KO) mice as an animal model of schizophrenia and autism. These mutant mice display a reduction in social behaviors; deficits in prepulse inhibition (PPI); reduced levels of parvalbumin-immunoreactive neurons in the medical prefrontal cortex, hippocampus, amygdala, and superior colliculus; and a deficit in of auditory phase-locked gamma oscillations. We found that oral administration of T-817MA ameliorated all these symptoms in the PDGFR-β KO mice. Furthermore, phase-locked gamma oscillations were significantly correlated with the density of parvalbumin-immunoreactive neurons, which was, in turn, correlated with PPI and behavioral parameters. These findings suggest that recovery of parvalbumin-immunoreactive neurons by pharmacological intervention relieved the reduction of phase-locked gamma oscillations and, consequently, ameliorated PPI and social behavioral deficits. Thus, our findings suggest that phase-locked gamma oscillations could be a useful physiological biomarker for abnormality of parvalbumin-immunoreactive neurons that may induce cognitive deficits and negative symptoms of schizophrenia and autism, as well as of effective pharmacological interventions in both humans and experimental animals.
authors: System Emotional Science, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Sugitani 2630, Toyama, Japan.
authors: Tomoya
authors: T
authors: Nakamura
authors: Department of Pathology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Sugitani 2630, Toyama, Japan.
authors: Jumpei
authors: J
authors: Matsumoto
authors: System Emotional Science, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Sugitani 2630, Toyama, Japan.
authors: Yusaku
authors: Y
authors: Takamura
authors: Department of Pathology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Sugitani 2630, Toyama, Japan.
authors: Yoko
authors: Y
authors: Ishii
authors: Department of Pathology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Sugitani 2630, Toyama, Japan.
authors: Masakiyo
authors: M
authors: Sasahara
authors: System Emotional Science, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Sugitani 2630, Toyama, Japan.
authors: Taketoshi
authors: T
authors: Ono
authors: System Emotional Science, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Sugitani 2630, Toyama, Japan.
authors: Hisao
authors: H
authors: Nishijo
mesh_terms: D000818:Animals; D001321:Autistic Disorder / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D059330:GABAergic Neurons / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D007150:Immunohistochemistry; D007398:Interpersonal Relations; D008297:Male; D008298:Maleates / Q000494:pharmacology; D051379:Mice; D018345:Mice, Knockout; D023421:Models, Animal; D010320:Parvalbumins / Q000276:immunology*; D017397:Prefrontal Cortex / Q000378:metabolism / Q000473:pathology; D065808:Prepulse Inhibition / Q000187:drug effects; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000235:genetics*; D012559:Schizophrenia / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D013876:Thiophenes / Q000494:pharmacology
chemical_list: C503102:1-(3-(2-(1-benzothiophen-5-yl) ethoxy) propyl)-3-azetidinol maleate; D008298:Maleates; D010320:Parvalbumins; D013876:Thiophenes; D020797:Receptor, Platelet-Derived Growth Factor beta