Andrea Balla , Stephen D. Ginsberg , Atheir I. Abbas , Henry Sershen , Daniel C. Javitt
{"title":"丝氨酸消旋酶敲除小鼠n -甲基-d-天冬氨酸受体功能障碍的翻译神经生理生物标志物","authors":"Andrea Balla , Stephen D. Ginsberg , Atheir I. Abbas , Henry Sershen , Daniel C. Javitt","doi":"10.1016/j.bionps.2020.100019","DOIUrl":null,"url":null,"abstract":"<div><p>Alterations in glutamatergic function are well established in schizophrenia (Sz), but new treatment development is hampered by the lack of translational pathophysiological and target engagement biomarkers as well as by the lack of animal models that recapitulate the pathophysiological features of Sz. Here, we evaluated the rodent auditory steady state response (ASSR) and long-latency auditory event-related potential (aERP) as potential translational markers. These biomarkers were assessed for their sensitivity to both the N-methyl-<span>d</span>-aspartate receptor (NMDAR) antagonist phencyclidine (PCP) and to knock-out (KO) of Serine Racemase (SR), which is known to lead to Sz-like alterations in function of parvalbumin (PV)-type cortical interneurons. PCP led to significant increases of ASSR that were further increased in SRKO-/-, consistent with PV interneuron effects. Similar effects were observed in mice with selective NMDAR KO on PV interneurons. By contrast, PCP but not SRKO reduced the amplitude of the rodent analog of the human N1 potential. Overall, these findings support use of rodent ASSR and long-latency aERP, along with previously described measures such as mismatch negativity (MMN), as translational biomarkers, and support SRKO mice as a potential rodent model for PV interneuron dysfunction in Sz.</p></div>","PeriodicalId":52767,"journal":{"name":"Biomarkers in Neuropsychiatry","volume":null,"pages":null},"PeriodicalIF":0.0000,"publicationDate":"2020-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.bionps.2020.100019","citationCount":"8","resultStr":"{\"title\":\"Translational neurophysiological biomarkers of N-methyl-d-aspartate receptor dysfunction in serine racemase knockout mice\",\"authors\":\"Andrea Balla , Stephen D. Ginsberg , Atheir I. Abbas , Henry Sershen , Daniel C. Javitt\",\"doi\":\"10.1016/j.bionps.2020.100019\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>Alterations in glutamatergic function are well established in schizophrenia (Sz), but new treatment development is hampered by the lack of translational pathophysiological and target engagement biomarkers as well as by the lack of animal models that recapitulate the pathophysiological features of Sz. Here, we evaluated the rodent auditory steady state response (ASSR) and long-latency auditory event-related potential (aERP) as potential translational markers. These biomarkers were assessed for their sensitivity to both the N-methyl-<span>d</span>-aspartate receptor (NMDAR) antagonist phencyclidine (PCP) and to knock-out (KO) of Serine Racemase (SR), which is known to lead to Sz-like alterations in function of parvalbumin (PV)-type cortical interneurons. PCP led to significant increases of ASSR that were further increased in SRKO-/-, consistent with PV interneuron effects. Similar effects were observed in mice with selective NMDAR KO on PV interneurons. By contrast, PCP but not SRKO reduced the amplitude of the rodent analog of the human N1 potential. Overall, these findings support use of rodent ASSR and long-latency aERP, along with previously described measures such as mismatch negativity (MMN), as translational biomarkers, and support SRKO mice as a potential rodent model for PV interneuron dysfunction in Sz.</p></div>\",\"PeriodicalId\":52767,\"journal\":{\"name\":\"Biomarkers in Neuropsychiatry\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2020-06-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://sci-hub-pdf.com/10.1016/j.bionps.2020.100019\",\"citationCount\":\"8\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Biomarkers in Neuropsychiatry\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S2666144620300095\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"Medicine\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Biomarkers in Neuropsychiatry","FirstCategoryId":"1085","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2666144620300095","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"Medicine","Score":null,"Total":0}
Translational neurophysiological biomarkers of N-methyl-d-aspartate receptor dysfunction in serine racemase knockout mice
Alterations in glutamatergic function are well established in schizophrenia (Sz), but new treatment development is hampered by the lack of translational pathophysiological and target engagement biomarkers as well as by the lack of animal models that recapitulate the pathophysiological features of Sz. Here, we evaluated the rodent auditory steady state response (ASSR) and long-latency auditory event-related potential (aERP) as potential translational markers. These biomarkers were assessed for their sensitivity to both the N-methyl-d-aspartate receptor (NMDAR) antagonist phencyclidine (PCP) and to knock-out (KO) of Serine Racemase (SR), which is known to lead to Sz-like alterations in function of parvalbumin (PV)-type cortical interneurons. PCP led to significant increases of ASSR that were further increased in SRKO-/-, consistent with PV interneuron effects. Similar effects were observed in mice with selective NMDAR KO on PV interneurons. By contrast, PCP but not SRKO reduced the amplitude of the rodent analog of the human N1 potential. Overall, these findings support use of rodent ASSR and long-latency aERP, along with previously described measures such as mismatch negativity (MMN), as translational biomarkers, and support SRKO mice as a potential rodent model for PV interneuron dysfunction in Sz.