Cytoskeletal changes in the brains of mice lacking calcineurin A alpha.
J Neurochem
; 68(4): 1668-78, 1997 Apr.
Article
en En
| MEDLINE
| ID: mdl-9084440
Hyperphosphorylated tau, the major component of the paired helical filaments of Alzheimer's disease, was found to accumulate in the brains of mice in which the calcineurin A alpha gene was disrupted [calcineurin A alpha knockout (CNA alpha -/-)]. The hyperphosphorylation involved several sites on tau, especially the Ser396 and/or Ser404 recognized by the PHF-1 monoclonal antibody. The increase in phosphorylated tau content occurred primarily in the mossy fibers of the CNA alpha -/- hippocampus, which contained the highest level of calcineurin in brains of wild-type mice. The CNA alpha -/- mossy fibers also contained less neurofilament protein than normal, although the overall level of neurofilament phosphorylation was unchanged. In the electron microscope, the mossy fibers of CNA alpha -/- mice exhibited abnormalities in their cytoskeleton and a lower neurofilament/microtubule ratio than those of wild-type animals. These findings indicate that hyperphosphorylated tau can accumulate in vivo as a result of reduced calcineurin activity and is accompanied by cytoskeletal changes that are likely to have functional consequences on the affected neurons. The CNA alpha -/- mice were found in a separate study to have deficits in learning and memory that may result in part from the cytoskeletal changes in the hippocampus.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Citoesqueleto
/
Química Encefálica
/
Proteínas de Unión a Calmodulina
/
Fosfoproteínas Fosfatasas
Límite:
Animals
Idioma:
En
Revista:
J Neurochem
Año:
1997
Tipo del documento:
Article
País de afiliación:
Estados Unidos
Pais de publicación:
Reino Unido