Distribution of tau protein kinase I/glycogen synthase kinase-3beta, phosphatases 2A and 2B, and phosphorylated tau in the developing rat brain.

When trying to elucidate the role played by tau protein kinase I/glycogen synthase kinase-3beta (TPKI/GSK-3beta) in tau phosphorylation, it is important to consider the balance that exists between the various kinases and phosphatases that are involved in vivo. We studied developmental changes in the expressions of TPKI/GSK-3beta and phosphatases 2A and 2B in rat brains using immunoblot analysis. The expression of the kinase peaked postnatally at days 8-11 and returned then to low level after 5 weeks. Phosphatase 2A showed a similar pattern, increasing postnatally until day 14 and decreasing thereafter. On the other hand, phosphatase 2B was undetectable at the juvenile stage, but later its presence increased rapidly to peak at 5 weeks after birth, after which it was maintained at high levels throughout the adult stage. Immunohistochemical studies using the PAP method revealed details of the distribution of TPKI/GSK-3beta. At postnatal days 3-21 both gray and white matter were immunoreactive. Later, after 5 weeks, the immunoreactivity became more restricted to the gray matter. The staining of tau phosphorylated at Ser 199, Ser 396, and Ser 413 followed mostly the pattern of the kinase distribution throughout all stages of development. These data, therefore, confirm that TPKI/GSK-3beta is expressed primarily in neurons and especially in neurites until postnatal day 21, whereafter the distribution is concentrated mostly in the cell soma and the proximal neurite region.