Developmental expression of tau proteins in the chicken and rat brain: rapid down-regulation of a paired helical filament epitope in the rat cerebral cortex coincides with the transition from immature to adult tau isoforms.

The monoclonal antibodies TAU-1 and AT8 are directed at human microtubule-associated protein tau epitopes that contain a dephosphorylated and phosphorylated Ser202, respectively, while AT180 and AT270 are anti-tau monoclonals with epitopes that require phosphorylated Thr181 and Thr231, respectively. We used these antibodies to study the developmental profiles of tau proteins in rat cerebral cortex and chicken optic lobes. In tau extracts from perinatal rat cerebral cortex. AT8 recognized one major protein band of approximately 50 kDa that peaks on postnatal day 6 and declines rapidly to lower levels at day 12. At later stages, the AT8 epitope was expressed by several adult tau isoforms that were, however, stained only very faintly in highly enriched samples. Two additional tau epitopes recognized by AT180 and AT270 were found to be expressed by one or two protein bands up to about postnatal day 19 and then declined. Unlike the AT8 epitope, in the mature brain these epitopes were stained strongly in enriched samples, where they were expressed by a greater number of adult isoforms. Between embryonic day 19 and postnatal day 12, TAU-1 was found to recognize one major protein band of approximately 50 kDa which migrated slightly faster than the AT8-binding band. At postnatal day 19 and all older stages (including adult cortex), at least three additional TAU-1-binding isoforms with higher apparent molecular weights were present. Hence, the transition from one immature to several adult TAU-1-binding tau isoforms between postnatal day 12 and 19 in rat cerebral cortex coincides with the phase of rapid down-regulation of the AT8 epitope. As in the rat cerebrum, in chicken optic lobes there is a developmental decrease of AT8-binding proteins which is paralleled by striking changes in the electrophoretic pattern of tau isoforms recognized by TAU-1. In both rat cerebral cortex and chicken optic lobes, the period of maximal expression of AT8-binding tau is morphologically characterized by intense axonal growth and beginning synaptogenesis, whereas its subsequent rapid down-regulation and the appearance of novel TAU-1-binding isoforms correlates with synaptic maturation, the onset of spontaneous electrical activity and the beginning of myelination.