- Email: [email protected]
Olanzapine treatment induces Olig2 cell proliferation in the hypothalamus with weight gain and enlarged fat tissues
e312
Abstracts / Neuroscience Research 68S (2010) e223–e334
P2-o18 Olanzapine treatment induces Olig2 cell proliferation in the hypothalamus with weight gain and enlarged fat tissues
After last injection, brains from all pups were harvested and used for Western blotting to determine protein expressions in the brain. Our preliminary data revealed that female pups received polyI:C injections showed significantly less weight gain than their controls, whereas male pups did not exhibit such difference. Further experiments are in progress to elucidate protein expression and the gene-environment interaction in these mice.
1
Dept Psychiatry, Univ of Nara Med, Kashihara, Nara 2 Dept Anatomy2, Univ of Nara Med, Kashihara, Nara
doi:10.1016/j.neures.2010.07.1386
Atypical antipsychotics are increasingly used in treating schizophrenic patients these days. Among these atypical antipsychotics, chronic treatment with olanzapine or clozapine frequently results in unwanted weight gain, hyperlipidemia and impaired glucose tolerance. The mechanisms underlying these side effects remain to be solved. In the present study, we focused on the weight gain, which lowers drug compliances in patients. Olanzapine-treated adult mice showed significant weight gain and Olig2 progenitor proliferation in the hypothalamus as compared to control-mice with an onset at 6th week of treatment. These mice have significantly larger fat tissues than the control mice. We are now examining the relationship between olanzapine administration and fat tissue-derived factors such as leptin and adiponectin. We also investigate energy balance of the olanzapine-treated mice.
P2-021 Event-related potential study of early visual processing in schizophrenia patients: links to cognitive symptoms
Takahira Yamauchi 1 , Kouko Tatsumi 2 , Hiroaki Okuda 2 , Manabu Makinodan 1 , Daisuke Ikawa 1 , Naoya Hirota 1 , Hiroki Yoshino 1 , Miyuki Sadamatsu 1 , Toshifumi Kishimoto 1 , Akio Wanaka 2
doi:10.1016/j.neures.2010.07.1384
P2-o19 Effects of antipsychotic medication on oligodendrocyte progenitor cell (OPC) in vitro Sohei Kimoto 1 , Michihiro Toritsuka 1 , Tomohiko Takeda 1 , Shinichi Fukami 1 , Manabu Makinodan 1 , Aya Okuda 2 , Hiroaki Okuda 2 , Kouko Tatsumi 2 , Akio Wanaka 2 , Toshifumi Kishimoto 1 1
Department of Psychiatry, Nara Medical University Anatomy and Neuroscience, Nara Medical University
2
Department of
In the developing brain, oligodendrocyte progenitor cells (OPCs) proliferate, migrate, and differentiate into mature oligodendrocytes (OLGs) capable of myelinating axons. Recently, OPCs have been identified as an abundant and widespread population in the adult as well as in the developing animal. Current research favors the hypothesis that these OPCs in the adult brain are able to proliferate and differentiate into myelinating OLGs as in development. We have reported oligodendrocyte dysfunction in the animal model for schizophrenia. If altered OLG function is an etiological factor or involved in the pathogenesis of schizophrenia, OPCs may respond to antipsychotic treatment under both in vitro and in vivo conditions during recovery process. In the present study, we obtained OPCs from optic nerve of P1-2 Wistar rat pups and examined effects of antipsychotics on OPCs in vitro. Olanzapine significantly increased the viable cell number of OPCs when compared with haloperidol in the WST-8 assay and BrdU incorporation analysis.These findings suggest a new neural mechanism of antipsychotic action of antipsychotics and help to establish a role for oligodendrocyte-lineage cells in the etiopathology and treatment of schizophrenia. doi:10.1016/j.neures.2010.07.1385
P2-o20 An investigation of neonatal immune challenge in NRG1 mutant mice
Sin-Ru Jhang 1 , Yao-Chu Chen 1 , Wan-Ting Chang 1 , Ju-Chun Pei 1 , Wen-Sung Lai 1,2
Shoji Tanaka 1 , Yosuke Maezawa 1 , Chisako Ikeda 2 , Eiji Kirino 2 1
Japan 2 Japan
Background: Cognitive impairment is one of the core symptoms of schizophrenia. Patients with schizophrenia also have deficits in early processing of visual information and other modalities of information. However, the link between them has not been clearly shown yet. We have addressed this issue by examining P100 and N200 ERP components in schizophrenia patients. Methods: Illusory contour (IC), no contour (NC), and real contour (RC) stimuli were presented to medicated schizophrenia patients (n = 20) and healthy controls (n = 20). Electroencephalograms were recorded at 19 sites using the standard 10–20 system. The data of P100 and N200 at P3, P4, O1, O2, T5, and T6, where the peak amplitudes for IC were large, were analyzed. Multiple regression with a PANSS five-factor model (cognitive, positive, negative, emotional, and excitation) has derived linear regression models for both the event-related potentials (ERPs) and the symptom factors. Results: The P100 component showed longer latency for IC in the patients. The N200 mean amplitudes were reduced in the patients. In contrast, a difference in the P100 mean amplitude between the groups was obscured by unclear wave forms of the P100 potential. We observed the diminished N200 amplitudes at the posterior and temporal electrodes in the patients, indicating impaired top-down modulation. The multiple regression analysis has derived statistically valid regression models of P100 and N200 for NC against cognitive symptoms. Conclusion: Among the five symptom factors, ERPs of early visual processing of complex objects are selectively linked to cognitive symptoms. Further refinement of the multiple regression models obtained in this study would be able to describe the relationships between the the symptoms and the aspects of information processing deficits. doi:10.1016/j.neures.2010.07.1387
P2-o22 Dysbindin1 and NRG1 genes expression in immortalized lymphocytes from patients with schizophrenia Hidenaga Yamamori 1,2 , Ryota Hashimoto 2,3 , Hironori Takamura 2 , Verrall Louise 2 , Yuka Yasuda 2 , Kazutaka Ohi 2 , Motoyuki Fukumoto 2 , Akira Ito 1 , Masatoshi Takeda 2 1 Department of Molecular Neuropsychiatry, Osaka University Graduate School of Medicine, Osaka, Japan 2 Department of Psychiatry, Osaka University Graduate School of Medicine, Osaka, Japan 3 Molecular Research Center for Children’s Mental Development, United Graduate School of Child Development, Osaka University, Kanazawa University and Hamamatsu University School of Medicine, Japan
1
Psychology, National Taiwan University 2 Neurobiology and Cognitive Science Center, National Taiwan University, Taiwan Schizophrenia appears to be a multifactorial disorder with a strong genetic predisposition. Accumulating evidence suggests that multiple susceptibility genes might contribute to the pathogenesis of schizophrenia, including NRG1 (neuregulin 1). While evidence indicates a genetic basis for schizophrenia, the concordance rate in homozygotic twins inflicting schizophrenia never reaches 50%, suggesting epigenetic involvement in this disorder, especially during early development. Early infection-induced disruption of neurodevelopment may predispose the organism to long-lasting changes and lead to the onset of schizophrenia in later life. The objective of this study is to examine whether early infection alone or its interaction with NRG1 deficiency could be pertinent to the vulnerability of schizophrenia-like endophenotypes and neurochemical abnormalities in mice. NRG1 heterozygous pups and wildtype littermate controls were generated from NRG1 heterozygous breeding pairs. Neonatal heterozygous and wild-type pups received daily injections of polyriboinosinic-polyribocytidylic (polyI:C) acid (5 mg/kg, s.c.) from postnatal day 2–6 to induce cytokine-associated viral-like responses. Their body temperature and body weights were monitored during this period of time.
Dysbindin1 and NRG1 genes are reported to be related to schizophrenia. Expression studies in post-mortem brains have also reported a lower or a higher expression of Dysbindin1 and NRG1, respectively, in schizophrenia. Post-mortem brain tissues are not easy to obtain. Moreover, post-mortem brain tissues could be very heterogeneous with regards to biochemical, lifetime medications absorbed and physiological status at the time of death and sampling. In contrast, medication and environmental influences that could mask the genetic basis of differences in RNA expression are removed by culturing in immortalized lymphocytes. Immortalized lymphocytes are readily obtained, thereby allowing larger case-control expression studies with optimal matching on key variables such as age and sex. But only a few microarray analysis studies using immortalized lymphocytes from patients with schizophrenia were reported so far. It is still controversial whether immortalized lymphocyte is an appropriate alternative to neuronal tissue. Recent study using microarray analysis has shown that Dysbindin1 and NRG1 genes expression in immortalized lymphocyte from patients with schizophrenia are decreased. In this study, we have measured Dysbindin1 and NRG1 genes expression in immortalized lymphocyte from 45 patients with schizophrenia and 45 controls using real-time quantitative RT-PCR that
Abstracts / Neuroscience Research 68S (2010) e223–e334
P2-o18 Olanzapine treatment induces Olig2 cell proliferation in the hypothalamus with weight gain and enlarged fat tissues
After last injection, brains from all pups were harvested and used for Western blotting to determine protein expressions in the brain. Our preliminary data revealed that female pups received polyI:C injections showed significantly less weight gain than their controls, whereas male pups did not exhibit such difference. Further experiments are in progress to elucidate protein expression and the gene-environment interaction in these mice.
1
Dept Psychiatry, Univ of Nara Med, Kashihara, Nara 2 Dept Anatomy2, Univ of Nara Med, Kashihara, Nara
doi:10.1016/j.neures.2010.07.1386
Atypical antipsychotics are increasingly used in treating schizophrenic patients these days. Among these atypical antipsychotics, chronic treatment with olanzapine or clozapine frequently results in unwanted weight gain, hyperlipidemia and impaired glucose tolerance. The mechanisms underlying these side effects remain to be solved. In the present study, we focused on the weight gain, which lowers drug compliances in patients. Olanzapine-treated adult mice showed significant weight gain and Olig2 progenitor proliferation in the hypothalamus as compared to control-mice with an onset at 6th week of treatment. These mice have significantly larger fat tissues than the control mice. We are now examining the relationship between olanzapine administration and fat tissue-derived factors such as leptin and adiponectin. We also investigate energy balance of the olanzapine-treated mice.
P2-021 Event-related potential study of early visual processing in schizophrenia patients: links to cognitive symptoms
Takahira Yamauchi 1 , Kouko Tatsumi 2 , Hiroaki Okuda 2 , Manabu Makinodan 1 , Daisuke Ikawa 1 , Naoya Hirota 1 , Hiroki Yoshino 1 , Miyuki Sadamatsu 1 , Toshifumi Kishimoto 1 , Akio Wanaka 2
doi:10.1016/j.neures.2010.07.1384
P2-o19 Effects of antipsychotic medication on oligodendrocyte progenitor cell (OPC) in vitro Sohei Kimoto 1 , Michihiro Toritsuka 1 , Tomohiko Takeda 1 , Shinichi Fukami 1 , Manabu Makinodan 1 , Aya Okuda 2 , Hiroaki Okuda 2 , Kouko Tatsumi 2 , Akio Wanaka 2 , Toshifumi Kishimoto 1 1
Department of Psychiatry, Nara Medical University Anatomy and Neuroscience, Nara Medical University
2
Department of
In the developing brain, oligodendrocyte progenitor cells (OPCs) proliferate, migrate, and differentiate into mature oligodendrocytes (OLGs) capable of myelinating axons. Recently, OPCs have been identified as an abundant and widespread population in the adult as well as in the developing animal. Current research favors the hypothesis that these OPCs in the adult brain are able to proliferate and differentiate into myelinating OLGs as in development. We have reported oligodendrocyte dysfunction in the animal model for schizophrenia. If altered OLG function is an etiological factor or involved in the pathogenesis of schizophrenia, OPCs may respond to antipsychotic treatment under both in vitro and in vivo conditions during recovery process. In the present study, we obtained OPCs from optic nerve of P1-2 Wistar rat pups and examined effects of antipsychotics on OPCs in vitro. Olanzapine significantly increased the viable cell number of OPCs when compared with haloperidol in the WST-8 assay and BrdU incorporation analysis.These findings suggest a new neural mechanism of antipsychotic action of antipsychotics and help to establish a role for oligodendrocyte-lineage cells in the etiopathology and treatment of schizophrenia. doi:10.1016/j.neures.2010.07.1385
P2-o20 An investigation of neonatal immune challenge in NRG1 mutant mice
Sin-Ru Jhang 1 , Yao-Chu Chen 1 , Wan-Ting Chang 1 , Ju-Chun Pei 1 , Wen-Sung Lai 1,2
Shoji Tanaka 1 , Yosuke Maezawa 1 , Chisako Ikeda 2 , Eiji Kirino 2 1
Japan 2 Japan
Background: Cognitive impairment is one of the core symptoms of schizophrenia. Patients with schizophrenia also have deficits in early processing of visual information and other modalities of information. However, the link between them has not been clearly shown yet. We have addressed this issue by examining P100 and N200 ERP components in schizophrenia patients. Methods: Illusory contour (IC), no contour (NC), and real contour (RC) stimuli were presented to medicated schizophrenia patients (n = 20) and healthy controls (n = 20). Electroencephalograms were recorded at 19 sites using the standard 10–20 system. The data of P100 and N200 at P3, P4, O1, O2, T5, and T6, where the peak amplitudes for IC were large, were analyzed. Multiple regression with a PANSS five-factor model (cognitive, positive, negative, emotional, and excitation) has derived linear regression models for both the event-related potentials (ERPs) and the symptom factors. Results: The P100 component showed longer latency for IC in the patients. The N200 mean amplitudes were reduced in the patients. In contrast, a difference in the P100 mean amplitude between the groups was obscured by unclear wave forms of the P100 potential. We observed the diminished N200 amplitudes at the posterior and temporal electrodes in the patients, indicating impaired top-down modulation. The multiple regression analysis has derived statistically valid regression models of P100 and N200 for NC against cognitive symptoms. Conclusion: Among the five symptom factors, ERPs of early visual processing of complex objects are selectively linked to cognitive symptoms. Further refinement of the multiple regression models obtained in this study would be able to describe the relationships between the the symptoms and the aspects of information processing deficits. doi:10.1016/j.neures.2010.07.1387
P2-o22 Dysbindin1 and NRG1 genes expression in immortalized lymphocytes from patients with schizophrenia Hidenaga Yamamori 1,2 , Ryota Hashimoto 2,3 , Hironori Takamura 2 , Verrall Louise 2 , Yuka Yasuda 2 , Kazutaka Ohi 2 , Motoyuki Fukumoto 2 , Akira Ito 1 , Masatoshi Takeda 2 1 Department of Molecular Neuropsychiatry, Osaka University Graduate School of Medicine, Osaka, Japan 2 Department of Psychiatry, Osaka University Graduate School of Medicine, Osaka, Japan 3 Molecular Research Center for Children’s Mental Development, United Graduate School of Child Development, Osaka University, Kanazawa University and Hamamatsu University School of Medicine, Japan
1
Psychology, National Taiwan University 2 Neurobiology and Cognitive Science Center, National Taiwan University, Taiwan Schizophrenia appears to be a multifactorial disorder with a strong genetic predisposition. Accumulating evidence suggests that multiple susceptibility genes might contribute to the pathogenesis of schizophrenia, including NRG1 (neuregulin 1). While evidence indicates a genetic basis for schizophrenia, the concordance rate in homozygotic twins inflicting schizophrenia never reaches 50%, suggesting epigenetic involvement in this disorder, especially during early development. Early infection-induced disruption of neurodevelopment may predispose the organism to long-lasting changes and lead to the onset of schizophrenia in later life. The objective of this study is to examine whether early infection alone or its interaction with NRG1 deficiency could be pertinent to the vulnerability of schizophrenia-like endophenotypes and neurochemical abnormalities in mice. NRG1 heterozygous pups and wildtype littermate controls were generated from NRG1 heterozygous breeding pairs. Neonatal heterozygous and wild-type pups received daily injections of polyriboinosinic-polyribocytidylic (polyI:C) acid (5 mg/kg, s.c.) from postnatal day 2–6 to induce cytokine-associated viral-like responses. Their body temperature and body weights were monitored during this period of time.
Dysbindin1 and NRG1 genes are reported to be related to schizophrenia. Expression studies in post-mortem brains have also reported a lower or a higher expression of Dysbindin1 and NRG1, respectively, in schizophrenia. Post-mortem brain tissues are not easy to obtain. Moreover, post-mortem brain tissues could be very heterogeneous with regards to biochemical, lifetime medications absorbed and physiological status at the time of death and sampling. In contrast, medication and environmental influences that could mask the genetic basis of differences in RNA expression are removed by culturing in immortalized lymphocytes. Immortalized lymphocytes are readily obtained, thereby allowing larger case-control expression studies with optimal matching on key variables such as age and sex. But only a few microarray analysis studies using immortalized lymphocytes from patients with schizophrenia were reported so far. It is still controversial whether immortalized lymphocyte is an appropriate alternative to neuronal tissue. Recent study using microarray analysis has shown that Dysbindin1 and NRG1 genes expression in immortalized lymphocyte from patients with schizophrenia are decreased. In this study, we have measured Dysbindin1 and NRG1 genes expression in immortalized lymphocyte from 45 patients with schizophrenia and 45 controls using real-time quantitative RT-PCR that