Abstract
Huntington’s disease (HD) is hereditary disease, caused by an expanded trinucleotide repeat, which produces cognitive and motor defects, and premature death. Several mouse models have been produced to understand the cause and progression of the disease. However, these models have a short lifespan, and their brains are relatively small with respect to microsurgery. Recently, a homozygote rat model, transgenic for HD, which develops symptoms similar to the late onset form of the disease, has been produced.
The major objective of this study was to evaluate the integrity of the frontal cortico-striatal projection system in a transgenic rat model of HD, by assessing the loss of pyramidal cells in the frontal cortex in this model. We address the hypothesis that corticostriatal projections are reduced in old, symptomatic, transgenic HD rats as found in humans with the disease. We injected the tracer biotinylated dextran amine into the dorsomedial striatum in old transgenic rats (n = 4) and wildtype controls (n = 3), and counted the number of retrogradely labelled neurons in the medial prefrontal cortex. Labelled cells were primarily found in the prelimbic, dorsal anterior cingulated, and medial precentral areas, in correspondence with the known topographical arrangement of frontal corticostriatal afferents.
When the number of labelled prefrontal corticostriatal cells per mm3 of injected tracer in the transgenic HD rat models was compared with the control rats, we observed a found significantly reduced numbers of labelled neurons in the prefrontal cortex (p = 0.033). However, given the small sample size, we concluded that further investigations are recommended.