title: Cognitive and socio-emotional deficits in platelet-derived growth factor receptor-β gene knockout mice.
abstract: Platelet-derived growth factor (PDGF) is a potent mitogen. Extensive in vivo studies of PDGF and its receptor (PDGFR) genes have reported that PDGF plays an important role in embryogenesis and development of the central nervous system (CNS). Furthermore, PDGF and the β subunit of the PDGF receptor (PDGFR-β) have been reported to be associated with schizophrenia and autism. However, no study has reported on the effects of PDGF deletion on mice behavior. Here we generated novel mutant mice (PDGFR-β KO) in which PDGFR-β was conditionally deleted in CNS neurons using the Cre/loxP system. Mice without the Cre transgene but with floxed PDGFR-β were used as controls. Both groups of mice reached adulthood without any apparent anatomical defects. These mice were further examined by conducting several behavioral tests for spatial memory, social interaction, conditioning, prepulse inhibition, and forced swimming. The test results indicated that the PDGFR-β KO mice show deficits in all of these areas. Furthermore, an immunohistochemical study of the PDGFR-β KO mice brain indicated that the number of parvalbumin (calcium-binding protein)-positive (i.e., putatively γ-aminobutyric acid-ergic) neurons was low in the amygdala, hippocampus, and medial prefrontal cortex. Neurophysiological studies indicated that sensory-evoked gamma oscillation was low in the PDGFR-β KO mice, consistent with the observed reduction in the number of parvalbumin-positive neurons. These results suggest that PDGFR-β plays an important role in cognitive and socioemotional functions, and that deficits in this receptor may partly underlie the cognitive and socioemotional deficits observed in schizophrenic and autistic patients.
authors: System Emotional Science, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan.
authors: Phuong Thi Hong
authors: PT
authors: Nguyen
authors: Tomoya
authors: T
authors: Nakamura
authors: Etsuro
authors: E
authors: Hori
authors: Susumu
authors: S
authors: Urakawa
authors: Teruko
authors: T
authors: Uwano
authors: Juanjuan
authors: J
authors: Zhao
authors: Ruixi
authors: R
authors: Li
authors: Nguyen Duy
authors: ND
authors: Bac
authors: Takeru
authors: T
authors: Hamashima
authors: Yoko
authors: Y
authors: Ishii
authors: Takako
authors: T
authors: Matsushima
authors: Taketoshi
authors: T
authors: Ono
authors: Masakiyo
authors: M
authors: Sasahara
authors: Hisao
authors: H
authors: Nishijo
mesh_terms: D000162:Acoustics; D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D001921:Brain / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D003072:Cognition Disorders / Q000235:genetics* / Q000503:physiopathology*; D003213:Conditioning, Psychological; D004644:Emotions / Q000502:physiology*; D005071:Evoked Potentials / Q000502:physiology; D005239:Fear / Q000502:physiology; D005615:Freezing; D055786:Gene Knockout Techniques; D051379:Mice; D018345:Mice, Knockout; D009043:Motor Activity / Q000502:physiology; D009474:Neurons / Q000378:metabolism; D009619:Nociceptors / Q000378:metabolism; D010320:Parvalbumins / Q000378:metabolism; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000172:deficiency / Q000235:genetics*; D013216:Reflex, Startle / Q000502:physiology; D012919:Social Behavior; D013550:Swimming / Q000502:physiology; D013997:Time Factors
chemical_list: D010320:Parvalbumins; D020797:Receptor, Platelet-Derived Growth Factor beta