Lessons learned from the transgenic Huntington's disease rats

Abstract

Huntington's disease (HD) is a fatal inherited disorder leading to selective neurodegeneration and neuropsychiatric symptoms. Currently, there is no treatment to slow down or to stop the disease. There is also no therapy to effectively reduce the symptoms. In the investigation of novel therapies, different animal models of Huntington's disease, varying from insects to nonhuman primates, have been created and used. Few years ago, the first transgenic rat model of HD, carrying a truncated huntingtin cDNA fragment with 51 CAG repeats under control of the native rat huntingtin promoter, was introduced. We have been using this animal model in our research and review here our experience with the behavioural, neurophysiological, and histopathological phenotype of the transgenic Huntington's disease rats with relevant literature.

Figure 1

Representative low-power photomicrographs of frontal brain sections stained for PGC-1α showing the subthalamic nucleus (STN) of a control and a transgenic HD rat. Note the increased number of PGC-1α-containing cells STN of the tgHD rat upon close inspection in comparison with the control subject. Scale bar is approximately 250 μm. The anatomical level is approximately anteroposterior −4.16 mm from bregma according to the rat brain atlas of Paxinos and Watson of 1998. Adopted from Vlamings et al. [8].

Figure 2

Representative photomicrographs of Nissl-stained frontal sections of the brains from a 12-month-old control rat and HD transgenic rat. Note the smaller striatum and the larger lateral ventricle (LV) (asterisk in b). The anatomical level is approximately anteroposterior 1.60 mm from bregma according to the rat brain atlas of Paxinos and Watson of 1998. Adopted from Kantor et al. [9].

Figure 3

Representative low-power photomicrographs of frontal brain sections stained for tyrosine hydroxylase (TH) showing the substantia nigra pars compacta (SNc), optic tract (OT), and a small part of the ventral tegmental area (VTA) of a control and a transgenic HD rat. Note the increased TH-containing cell density in the SNc of the transgenic HD rats upon close inspection. The high-power photomicrograph inset in the right upper corner shows a magnification of TH-containing cells of a transgenic rat. Scale bar is approximately 250 μm. The anatomical level is approximately anteroposterior −5.2 mm from Bregma according to the Paxinos and Watson atlas of 1998. Adopted from Jahanshahi et al. [10].