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Upregulation of α‐synuclein expression in the rat cerebellum in experimental hepatic encephalopathy
Author(s) -
Suárez I.,
Bodega G.,
Fernández B.
Publication year - 2010
Publication title -
neuropathology and applied neurobiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.538
H-Index - 95
eISSN - 1365-2990
pISSN - 0305-1846
DOI - 10.1111/j.1365-2990.2010.01083.x
Subject(s) - colocalization , cerebellum , glial fibrillary acidic protein , pathology , western blot , biology , blot , downregulation and upregulation , immunohistochemistry , neuropathology , microbiology and biotechnology , endocrinology , medicine , biochemistry , disease , gene
I. Suárez, G. Bodega and B. Fernández (2010) Neuropathology and Applied Neurobiology 36, 422–435
Upregulation of α‐synuclein expression in the rat cerebellum in experimental hepatic encephalopathyAims: The overexpression of α‐synuclein has been associated with neurodegenerative diseases, especially when the protein aggregates to form insoluble structures. The present study examined the effect of chronic hyperammonaemia on α‐synuclein expression in the rat cerebellum following portacaval anastomosis (PCA). Methods: Immunohistochemical and western blot determinations were performed 1 month and 6 months after the PCA procedure. Results: A time‐dependent increase in α‐synuclein expression was seen in the cerebellar grey matter compared with the controls. At 1 month post PCA, α‐synuclein‐immunopositive material was observed in the molecular layer, while the Purkinje cells showed weak α‐synuclein expression, and α‐synuclein aggregates were observed throughout the granular layer. At 6 months post PCA, α‐synuclein expression was significantly increased compared with the controls. α‐synuclein‐immunostained astroglial cells were also found; the Bergmann glial cells showed α‐synuclein‐positive processes in the molecular layer of PCA‐exposed rats, and in the granular layer, perivascular astrocytes showed intense α‐synuclein immunoreactivity, as indicated by colocalization of α‐synuclein with glial fibrillary acidic protein (GFAP). In addition, ubiquitin‐immunoreactive inclusions were present in PCA‐exposed rats, although they did not colocalize with α‐synuclein. Western blotting performed at 6 months post PCA showed a reduction in the level of soluble α‐synuclein compared with 1 month post PCA and the controls; this reduction was concomitant with an increase in the insoluble form of α‐synuclein. Conclusions: Although the precise mechanism by which α‐synuclein aggregates in PCA‐treated rats remains unknown, the present data suggest an important role for this protein in the onset and progression of hepatic encephalopathy, probably via its expression in astroglial cells.