B03 Behavioral characterization of homozygous BACHD rats

Abstract

Background Behavioral changes in Huntington’s disease (HD) are directly associated with the dysfunction and degeneration of certain brain areas, most prominently striatum and cortex. The sole cause of developing HD is the expansion of an unstable repeat of CAG base triplets in the coding region of the Huntingtin gene, HTT. The BACHD rat overexpresses full length human mutant huntingtin with 97 alternating CAA/CAG repeats and is thus a well suited genetic animal model of HD. Aims To analyze homozygous BACHD rats for motor, learning as well as memory deficits and compare data with results of heterozygous BACHD rats who are already well characterized for their behavioral phenotype. Methods Two and five months old homozygous animals were analyzed for motor as well as learning, memory and relearning deficits. Results Our results show motor deficits analyzed with the grip strength test and RotaRod in homozygous BACHD rats at the age of two and five months. Additional analyses in the Barnes maze test showed initial learning, memory and relearning deficits at the age of two months, which were further increased at the age of 5 months. Further analysis in the passive avoidance test revealed emotional learning deficits of 2 months old homozygous BACHD rats. Conclusions Our results show that homozygous BACHD rats present a very early motor and cognitive phenotype. Cognitive deficits already start at the young age of two months and therefore appear much earlier compared to heterozygous BACHD rats. Although homozygous animals need to be further characterized, our data already suggest that homozygous BACHD rats will be of great importance for future HD research. Testing new compounds that influence HD disease progression could be facilitated, since treatment could be significantly shortened compared to heterozygous BACHD rats.