caa a22 4500 606201270 CHVBK 20210128100947.0 cr unu---uuuuu 210128e20150101xx s 000 0 eng 10.1007/s00429-013-0638-z doi (NATIONALLICENCE)springer-10.1007/s00429-013-0638-z Schizophrenia-like phenotype of polysialyltransferase ST8SIA2-deficient mice [Elektronische Daten] [Tim Kröcher, Kristina Malinovskaja, Monika Jürgenson, Anu Aonurm-Helm, Tamara Zharkovskaya, Anti Kalda, Iris Röckle, Miriam Schiff, Birgit Weinhold, Rita Gerardy-Schahn, Herbert Hildebrandt, Alexander Zharkovsky] Posttranslational modification of the neural cell adhesion molecule (NCAM) by polysialic acid (polySia) is crucial for nervous system development and brain plasticity. PolySia attachment is catalyzed by the polysialyltransferases (polySTs) ST8SIA2 and ST8SIA4, two enzymes with distinct but also common functions during neurodevelopment and in the adult brain. A growing body of evidence links aberrant levels of NCAM and polySia as well as variation in the ST8SIA2 gene to neuropsychiatric disorders, including schizophrenia. To investigate whether polyST deficiency might cause a schizophrenia-like phenotype, St8sia2 −/− mice, St8sia4 −/− mice and their wildtype littermates were assessed neuroanatomically and subjected to tests of cognition and sensorimotor functions. St8sia2 −/− but not St8sia4 −/− mice displayed enlarged lateral ventricles and a size reduction of the thalamus accompanied by a smaller internal capsule and a highly disorganized pattern of fibers connecting thalamus and cortex. Reduced levels of the vesicular glutamate transporter VGLUT2 pointed towards compromised glutamatergic thalamocortical input into the frontal cortex of St8sia2 −/− mice. Both polyST-deficient lines were impaired in short- and long-term recognition memory, but only St8sia2 −/− mice displayed impaired working memory and deficits in prepulse inhibition. Furthermore, only the St8sia2 −/− mice exhibited anhedonic behavior and increased sensitivity to amphetamine-induced hyperlocomotion. These results reveal that reduced polysialylation in St8sia2 −/− mice leads to pathological brain development and schizophrenia-like behavior. We therefore propose that genetic variation in ST8SIA2 has the potential to confer a neurodevelopmental predisposition to schizophrenia. Springer-Verlag Berlin Heidelberg, 2013 Thalamocortical connectivity nationallicence Cortex nationallicence Working memory nationallicence Sensorimotor gating nationallicence Polysialic acid nationallicence Neural cell adhesion molecule (NCAM) nationallicence NCAM : Neural cell adhesion molecule nationallicence polySia : Polysialic acid nationallicence polyST : Polysialyltransferase nationallicence PPI : Prepulse inhibition nationallicence Rt : Reticular thalamic nucleus nationallicence VGLUT : Vesicular glutamate transporter nationallicence Kröcher Tim Institute of Cellular Chemistry (OE4330), Hannover Medical School, Carl-Neuberg-Str. 1, 30625, Hannover, Germany aut Malinovskaja Kristina Department of Pharmacology, Centre of Excellence for Translational Medicine, University of Tartu, Ravila 19, 50411, Tartu, Estonia aut Jürgenson Monika Department of Pharmacology, Centre of Excellence for Translational Medicine, University of Tartu, Ravila 19, 50411, Tartu, Estonia aut Aonurm-Helm Anu Department of Pharmacology, Centre of Excellence for Translational Medicine, University of Tartu, Ravila 19, 50411, Tartu, Estonia aut Zharkovskaya Tamara Department of Pharmacology, Centre of Excellence for Translational Medicine, University of Tartu, Ravila 19, 50411, Tartu, Estonia aut Kalda Anti Department of Pharmacology, Centre of Excellence for Translational Medicine, University of Tartu, Ravila 19, 50411, Tartu, Estonia aut Röckle Iris Institute of Cellular Chemistry (OE4330), Hannover Medical School, Carl-Neuberg-Str. 1, 30625, Hannover, Germany aut Schiff Miriam Institute of Cellular Chemistry (OE4330), Hannover Medical School, Carl-Neuberg-Str. 1, 30625, Hannover, Germany aut Weinhold Birgit Institute of Cellular Chemistry (OE4330), Hannover Medical School, Carl-Neuberg-Str. 1, 30625, Hannover, Germany aut Gerardy-Schahn Rita Institute of Cellular Chemistry (OE4330), Hannover Medical School, Carl-Neuberg-Str. 1, 30625, Hannover, Germany aut Hildebrandt Herbert Institute of Cellular Chemistry (OE4330), Hannover Medical School, Carl-Neuberg-Str. 1, 30625, Hannover, Germany aut Zharkovsky Alexander Department of Pharmacology, Centre of Excellence for Translational Medicine, University of Tartu, Ravila 19, 50411, Tartu, Estonia aut Brain Structure and Function Springer Berlin Heidelberg 220/1(2015-01-01), 71-83 1863-2653 220:1<71 2015 220 429 https://doi.org/10.1007/s00429-013-0638-z text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s00429-013-0638-z text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Kröcher Tim Institute of Cellular Chemistry (OE4330), Hannover Medical School, Carl-Neuberg-Str. 1, 30625, Hannover, Germany aut NATIONALLICENCE 700 1- Malinovskaja Kristina Department of Pharmacology, Centre of Excellence for Translational Medicine, University of Tartu, Ravila 19, 50411, Tartu, Estonia aut NATIONALLICENCE 700 1- Jürgenson Monika Department of Pharmacology, Centre of Excellence for Translational Medicine, University of Tartu, Ravila 19, 50411, Tartu, Estonia aut NATIONALLICENCE 700 1- Aonurm-Helm Anu Department of Pharmacology, Centre of Excellence for Translational Medicine, University of Tartu, Ravila 19, 50411, Tartu, Estonia aut NATIONALLICENCE 700 1- Zharkovskaya Tamara Department of Pharmacology, Centre of Excellence for Translational Medicine, University of Tartu, Ravila 19, 50411, Tartu, Estonia aut NATIONALLICENCE 700 1- Kalda Anti Department of Pharmacology, Centre of Excellence for Translational Medicine, University of Tartu, Ravila 19, 50411, Tartu, Estonia aut NATIONALLICENCE 700 1- Röckle Iris Institute of Cellular Chemistry (OE4330), Hannover Medical School, Carl-Neuberg-Str. 1, 30625, Hannover, Germany aut NATIONALLICENCE 700 1- Schiff Miriam Institute of Cellular Chemistry (OE4330), Hannover Medical School, Carl-Neuberg-Str. 1, 30625, Hannover, Germany aut NATIONALLICENCE 700 1- Weinhold Birgit Institute of Cellular Chemistry (OE4330), Hannover Medical School, Carl-Neuberg-Str. 1, 30625, Hannover, Germany aut NATIONALLICENCE 700 1- Gerardy-Schahn Rita Institute of Cellular Chemistry (OE4330), Hannover Medical School, Carl-Neuberg-Str. 1, 30625, Hannover, Germany aut NATIONALLICENCE 700 1- Hildebrandt Herbert Institute of Cellular Chemistry (OE4330), Hannover Medical School, Carl-Neuberg-Str. 1, 30625, Hannover, Germany aut NATIONALLICENCE 700 1- Zharkovsky Alexander Department of Pharmacology, Centre of Excellence for Translational Medicine, University of Tartu, Ravila 19, 50411, Tartu, Estonia aut NATIONALLICENCE 773 0- Brain Structure and Function Springer Berlin Heidelberg 220/1(2015-01-01), 71-83 1863-2653 220:1<71 2015 220 429