Vitamin A deficiency and behavioral and motor deficits in the human immunodeficiency virus type 1 transgenic rat

Abstract

The human immunodeficiency virus type 1 (HIV-1) transgenic (Tg) rat model incorporates a noninfectious viral genome that is under similar regulatory control mechanisms in vivo as those that exist with natural infection in humans. Vitamin A (VA) deficiency in humans has been associated with progressive systemic HIV disease and with impaired cognition in rodent models. The effects on of VA deficiency on the development of behavioral abnormalities with HIV infection have not been previously described. In these studies, wild-type (Wt) and Tg rats maintained on either a normal (VA+) or a VA-deficient (VA-) diet were examined for activity in an open field (horizontal activity, total distance, vertical activity, and rearing) and on rotarod testing. On both open field and rotarod testing, the Tg rats performed worse than the Wt rats, with the most severe deficits noted in the TgVA- animals. Analysis of the specific effects of the presence of the HIV transgene and the diet on the performance on the open field tests showed a dominant effect from the transgene on all of the tests, with an effect from the diet on only the number of rearings. On rotarod testing, effects form both the diet and the transgene were observed at lower speeds, at the highest speeds, and on the accelerating rotarod. These studies therefore demonstrate that behavioral and motor abnormalities can be detected in this model and are likely due to similar mechanisms by which humans infected with HIV might develop cognitive-motor impairment in association with VA deficiency.

Figure 1

Horizontal activity and total distance measurements for the HIV-1 transgenic (Tg) and the wild type (Wt) rats on the normal (VA+) or vitamin A deficient (VA−) diet. ** p< 0.01, respectively, when compared against wild-type animals with normal diet; †† p< 0.01, respectively, when compared against wild-type animals with vitamin A-deficient diet.

Figure 2

Vertical and rearing activity for the HIV-1 transgenic (Tg) and wild type (Wt) rats on the normal (VA+) or vitamin A deficient (VA−) diet. *, ** p< 0.05 and 0.01, respectively, when compared against wild-type animals with normal diet; †, †† p< 0.05 and 0.01, respectively, when compared against wild-type animals with vitamin A-deficient diet.

Figure 3

Rotarod performance for the Wt and Tg rats on the VA+ and VA− diets during training and at increasing rod speeds. At 12 rpm all of the Wt rats on the normal diet remained on the rotarod for the maximum time allowed (180 sec.). *, ** p< 0.05 and 0.01, respectively, when compared against wild-type animals with normal diet; †, †† p< 0.05 and 0.01, respectively, when compared against wild-type animals with vitamin A-deficient diet.

Figure 4

Performance by the Wt and Tg rats on the accelerating rotarod. *, ** p< 0.05 and 0.01, respectively, when compared against wild-type animals with normal diet; †, †† p< 0.05 and 0.01, respectively, when compared against wild-type animals with vitamin A-deficient diet.