Altered GABA distribution in hamster brain is an early molecular consequence of infection by scrapie prions.

Antibodies specific for GABA, glutamate and taurine were used to study the distribution of these amino acid neurotransmitters during the progression of scrapie in hamsters. Immunohistochemical distribution of glutamate and taurine were unaffected in scrapie hamsters compared with controls, but the distribution of GABA was altered by 21 days after inoculation. We found both a greater number of neurons showing GABA-like immunoreactivity and more intense staining in those neurons in scrapie-inoculated hamster brains, particularly in the hippocampus, inferior colliculus, frontal cortex and cerebellum. The overall concentrations of aspartate, GABA, glutamate and taurine, measured in seven different brain regions by PITC-amino acid analysis, were not significantly different between normal and scrapie-affected hamsters. The subtle alteration in GABA metabolism detected in this scrapie model suggests that PrPSc interacts directly with a component of the GABA system.