Tau mRNA isoforms following sciatic nerve axotomy with and without regeneration.

The microtubule-associated protein tau promotes the polymerization and stabilization of microtubules in normal neurons and is the main component of paired helical filaments, one of the pathological structures characteristic of Alzheimer's disease (AD). In adult neurons alternative splicing generates tau isoforms with 4 microtubule binding domains (4R tau) while tau in developing neurons contains only 3 such domains (3R tau). The extra microtubule binding domain confers adult tau with an increased ability to interact with and stabilize microtubules. We hypothesized that tau gene expression would revert to the developmental pattern following nerve injury. The sciatic nerve of adult rats was unilaterally crushed or transected and tau mRNA isoform expression in the spinal cord was examined by reverse transcriptase-polymerase chain reaction. At 2 and 3 days post-crush, both the 3R and 4R tau mRNA isoform levels on the injured side had decreased compared to the contralateral side. However, the ratio of 4R to 3R tau mRNA was not significantly different between the two sides at any post-crush time point examined. Following nerve transection, a significant increase in the 3R tau mRNA isoform on the transected compared to the contralateral side occurred at 14 days; the ratio of 4R to 3R tau mRNA was significantly decreased on the transected compared to the contralateral side at 7, 14 and 42 days. These results suggest that a recapitulation of the developmental pattern of 3R tau gene expression occurs following nerve transection but not nerve crush. Our results combined with the recent findings that the 3R tau protein isoform preferentially forms paired helical filament-like structures in vitro suggests that an increased expression of the 3R tau mRNA isoform may also occur in AD.