Myelin, oligodendrocytes and axonal pathology in ST8SIA2minus/minus mice, a model for schizophrenia research

• Autorzy: Wisniewska M.B. , Szewczyk L. , Hildebrandt H. , Kuznicki J.
• Języki publikacji: EN

Abstrakty

EN

Growing body of evidence implicates myelin and axon abnormalities in schizophrenia. Using a proteomic approach, we detected a decrease in myelin proteins in the hippocampus of St8sia2-/- mice that display behavioral and neuroanatomical features of schizophrenia. ST8SIA2 adds polysialic acid to neural cell adhesion molecule (NCAM), and this posttranslational modification is vital for development and plasticity in the brain. Polymorphisms in the ST8SIA2 gene and NCAM hyposialylation have been associated with schizophrenia. To gain an insight into the relationship between polysialylation state of NCAM and myelin we performed phenotypic analysis of St8sia2-/- mice, focusing on: myelin formation and maintenance, oligodendrocyte differentiation, and ultrastructure of axons. We applied several imaging techniques ranging from histological staining to electron microscopy, several immunodetection methods, and in vitro differentiation of oligodendrocyte precursors. Myelin formation was not delayed in the knockout mice, yet the levels of major myelin proteins were decreased from the early beginning (in 15-day-old mice) and it was accompanied by a lower number of oligodendrocytes. Moreover, in vitro differentiation of oligodendrocyte precursors was less efficient in the case of St8sia2-/- cells. Ultrastructure analysis of the nerve fibers showed thinning of the myelin sheath in 3-month-old mice. This phenotype was more severe in 8-month-old mice, with clear signs of axon degeneration and even lesions. We suppose that these late axonal pathologies are secondary to oligodendrocyte and myelin dysfunction. We conclude that the ST8SIA2-mediated polysialylation of NCAM plays a role in maintaining myelin and axonal integrity. The myelin phenotype in St8sia2-/- mice resembles white matter abnormalities in schizophrenia. ST8SIA2-deficient mice are a suitable model for better understanding schizophrenia-associated myelin and axonal pathology and to identify novel therapeutic targets.

• Wydawca: -
• Czasopismo: Acta Neurobiologiae Experimentalis
• Rocznik: 2015
• Tom: 75
• Numer: Supl.
• Opis fizyczny: p.S21

Twórcy

autor

Wisniewska M.B.

• International Institute of Molecular and Cell Biology, Warsaw, Poland
• Centre of New Technologies, University of Warsaw, Warsaw, Poland

autor

Szewczyk L.

• International Institute of Molecular and Cell Biology, Warsaw, Poland
• Centre of New Technologies, University of Warsaw, Warsaw, Poland

autor

Hildebrandt H.

• Hannover Medical School, Hannower, Germany

autor

Kuznicki J.

• International Institute of Molecular and Cell Biology, Warsaw, Poland