Altered expression of amyloid precursor proteins after traumatic brain injury in rats: In situ hybridization and immunohistochemical study

The expression of alternatively spliced mRNAs for amyloid precursor protein (APP) isoforms and their translation products were examined in the rat cer ebral cortex 1, 3, 6, and 12 h and 1, 3, and 7 days (12 = 4-5 in each group ) after fluid-percussion brain injury. In situ hybridization studies demons trated that the expression of APP695 mRNA decreased in and around the damag ed area of the cerebral cortex exposed to fluid-percussion injury 1 h after the insult. On the other hand, APP751/770 mRNAs were increased in the regi ons surrounding the damaged cortical areas 1 day after the injury. An incre ase of immunoreactive APP was detected in the regions around the damaged co rtical areas 3 h after traumatic injury and maintained for the following 3 days. The APP immunoreactivity in the damaged cortices declined to the leve l of sham-operated animals by post-experimental day 7, Using an anti-amyloi d beta (A beta) protein (17-24) antibody, no deposits of immunoreactive A b eta (17-24) were observed in any of the samples examined in these experimen ts. These results suggest that the induction of Kunitz-type protease inhibi tor (KPI) domain-containing APP mRNAs and the increased accumulation of APP are involved in the physiological and neuropathological responses of brain s under various neurodegenerative conditions, including head trauma.