In the mature rat dorsal root ganglion (DRG), only one tau isoform is expressed, and this protein (110 kDa in apparent molecular weight) is considerably larger in size than the predominant tau isoforms found in brain. The size of the mRNA encoding the "big" tau mRNA in DRG [approximately 8 kilobases (kb)] is also much larger than that of the major rat brain tau mRNA species (approximately 6 kb). In this study, we examined the pattern of normal developmental changes in expression of this high-molecular-weight (HMW) tau and its encoding mRNA and also determined how axonal injury of adult DRG neurons effected the expression of this gene. RNA blotting experiments revealed that higher levels of HMW tau mRNA were present in the DRG at early postnatal times than in the adult. Immunoblotting of total DRG protein using a monoclonal tau antibody revealed that the immature DRG (7 d postnatal) contained a 62-kDa tau isoform in addition to the HMW tau isoform that was expressed in the adult DRG. Neither of the tau isoforms expressed in the immature DRG was present to any significant extent in either immature or adult rat brain. To examine how tau expression changed in adult DRG neurons during regeneration, the sciatic nerves of rats were unilaterally crushed, and the L4 and L5 DRG were harvested 1, 7, and 14 d later.(ABSTRACT TRUNCATED AT 250 WORDS)

The microtubule associated protein called tau, found primarily in neurons, was detected in a human neuroblastoma cell line, LAN-5. Cells treated with retinoic acid (2.0 x 10(-5) M) differentiate and acquire processes similar to neurons. Differentiated and logarithmically growing undifferentiated cells were exposed to varying doses of doxorubicin (an anthracycline chemotherapeutic antibiotic). While doxorubicin was lethal to many undifferentiated dividing cells, it was not as damaging to differentiated cells. After 2 to 4 days of doxorubicin treatment, the cells were harvested, the protein concentration determined and SDS-PAGE performed. Proteins were blotted onto nitrocellulose paper and immunostained with either a rabbit antiserum or mouse monoclonal antibody to tau. Undifferentiated LAN-5 cells treated with 4.0 x 10(-8) M doxorubicin for 4 days and cells treated with 8.0 x 10(-8) M doxorubicin for 2 days displayed a distinct lower band (just below the 50 kd marker) that was either absent or very faint in untreated controls.