Dendritic and axonal distribution of the microtubule-associated proteins MAP2 and tau in the cerebellum of the nervous mutant mouse.
The fate of the different types of axons and dendrites in the nervous mutant mouse has been studied with antibodies raised against the two major microtubule-associated proteins, MAP2 and tau. These proteins are specific markers of dendrites and axons, respectively. (1) Immunoblot analysis of cerebellar extracts showed that MAP2 concentration is markedly reduced (by approximately 90%) in the adult mutant. A 60% decrease was already noticed at day 20 postnatal, i.e., when all the Purkinje cells are present in their normal location and in apparent normal number. (2) Immunohistochemical studies performed at an adult stage with anti MAP2 antibodies showed marked alterations in the shape of the dendrites of the rare surviving Purkinje cells present in the lateral sections of the cerebellum of the mutant. In the vermis, where 50% of the cells survive in adulthood, the MAP2 antibody revealed both clusters of cells with a normal density and an intricated and extensive pattern of dendritic arborization and isolated cells showing either an apparently normal or an altered dendritic tree. (3) At day 20 postnatal the same antibody revealed, in the lateral sections severe abnormalities of the dendrites of the Purkinje cells which were different from those seen in adulthood in the vermis. Thus, although few or any Purkinje cells are dead at this stage, a large proportion of them have already profound dendritic alterations. In contrast, in the vermis the Purkinje cells and their dendritic tree are undistinguishable at this stage from those of the unaffected normal mice. (4) Immunoblot and immunohistochemical studies performed with the anti Tau antibody suggested that the majority of the axonal fibers of the cerebellum were present both at day 20 postnatal and at later adult stages. This suggests that, although deprived of their postsynaptic targets these axons can survive for a long time after Purkinje cell death. However, an anti-neurofilament monoclonal antibody which stains specifically the axons of the basket cells, revealed an altered morphology of the basket cell nest in the regions devoid of Purkinje cells. (5) In conclusion the alterations in the morphology of dendrites seem to represent an early event of Purkinje cell degeneration and to be correlated with a marked decrease in expression of MAP2. It remains unclear, however, whether such changes in expression of MAP2 represent a primary effect of the mutation or if it is only a precocious result of Purkinje cell degeneration.
Brion
J P
JP
Laboratoire d'Anatomie Pathologique, Université Libre de Bruxelles, Belgium.
Guilleminot
J
J
Nunez
J
J
D000818:Animals; D001369:Axons / Q000378:metabolism*; D002531:Cerebellum / Q000254:growth & development / Q000378:metabolism*; D003712:Dendrites / Q000378:metabolism*; D051379:Mice; D008818:Mice, Neurologic Mutants / Q000378:metabolism*; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D016875:tau Proteins
D008869:Microtubule-Associated Proteins; D016875:tau Proteins