Preferencje help
Polish version English version Język
Widoczny [Schowaj] Abstrakt
Liczba wyników

Znaleziono wyników: 2

Liczba wyników na stronie
Pierwsza strona wyników Pięć stron wyników wstecz Poprzednia strona wyników Strona / 1 Następna strona wyników Pięć stron wyników wprzód Ostatnia strona wyników

Wyniki wyszukiwania

help Sortuj według:

help Ogranicz wyniki do:
Pierwsza strona wyników Pięć stron wyników wstecz Poprzednia strona wyników Strona / 1 Następna strona wyników Pięć stron wyników wprzód Ostatnia strona wyników
1

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

100%
Wisniewska M. B., Szewczyk L., Hildebrandt H., Kuznicki J.
Acta Neurobiologiae Experimentalis
|
2015
|
tom 75
|
nr Supl.
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.
2

ST8SIA2 gene deficiency leads to aged-related axonal degeneration and weakening of myelin sheath

64%
Szewczyk L., Brozko N., Nagalski A., Liszewska E., Zawadzka M., Hildebrandt H., Kuznicki J., Wisniewska M.
Acta Neurobiologiae Experimentalis
|
2015
|
tom 75
|
nr Supl.
BACKGROUND AND AIMS: This study was to investigate the involvement of ST8SIA2 in myelination of the brain. ST8SIA2 and its paralog ST8SIA4 synthesize polysialic acid chains (PSA) to NCAMs. Synthesis of PSA and its downregulation during brain development are crucial for a proper myelin formation. However, myelin forms normally in St8sia4-/- mice. So far, myelin-related phenotype of St8sia2-/- mice has not been investigated. METHODS: Mass-spectrometry, westernblot, myelin staining, immunostaining, electron microscopy RESULTS: Quantitative mass-spectrometry showed that the levels of myelin proteins MBP and PLP1 in the hippocampus are lower in adult St8sia2-/- mice than in control. Westernblot confirmed this result and revealed the same changes in cortical areas. Then, in order to determine the onset of the myelin impairment in the knockout mice, we labeled white matter in brain sections from mice at postnatal ages (P15 to P240) with Black Gold II, and showed that this phenotype develops with age. In agreement with this result, western blot analysis of major myelin proteins: PLP1, MBP, MOBP, MOG and CNPase, in the brain of mice from P15 to P90 revealed their lower levels in the knockouts, especially in the older mice. Electron microscopy revealed thinning of myelin sheath in the adult knockouts at P90 and P240, as well as abnormalities in axonal morphology and their degeneration at P240. Western blot revealed twofold lower levels of neurofilament proteins also suggesting axonopathy. CONCLUSIONS: ST8SIAII-mediated deficiency of polysialylation leads to axonal pathologies and their degeneration accompanied by myelin weakening. A decrease in polysialylated NCAM has been observed in postmortem schizophrenics brains, and the mice lacking the St8sia2 gene display schizophrenia-related behavior and anatomical abnormalities. We propose that myelin and axonal pathologies of schizophrenics might be a consequence of unsufficient level of polysialylation during development and in early adulthood.
Pierwsza strona wyników Pięć stron wyników wstecz Poprzednia strona wyników Strona / 1 Następna strona wyników Pięć stron wyników wprzód Ostatnia strona wyników
JavaScript jest wyłączony w Twojej przeglądarce internetowej. Włącz go, a następnie odśwież stronę, aby móc w pełni z niej korzystać.