Quantitation of parvalbumin+ neurons and human immunodeficiency virus type 1 (HIV-1) regulatory gene expression in the HIV-1 transgenic rat: effects of vitamin A deficiency and morphine

Abstract

Vitamin A (VA) deficiency in human immunodeficiency virus (HIV) infection has been associated with more progressive HIV disease, which may be enhanced by opioid use. In these studies, we examined the effects of VA deficiency and morphine on frontal cortex neuronal numbers in the HIV-1 transgenic (Tg) rat. These studies showed that total numbers of neurons were similar for rats on the VA-deficient diet as for rats on the normal diet and these numbers were not affected by treatment with morphine. In contrast, numbers of neurons that expressed the calcium-binding protein parvalbumin, which is a marker interneurons that express the inhibitory neurotransmitter gamma-aminobutyric acid (GABAergic neurons) were decreased for wild-type (Wt) rats on the VA-deficient diet and for Wt rats treated with morphine. In addition, parvalbumin+ neurons were also decreased for Tg rats on a normal diet but increased to normal levels when these animals were placed on the VA-deficient diet and treated with morphine. Analysis of expression of the genes that code for the HIV regulatory proteins vif, vpr, nef, and tat in frontal cortex and adjacent subcortical white matter showed that tat expression was increased in the morphine-treated Tg rat on the VA-deficient diet as compared to untreated Tg rats on the normal diet and untreated VA-deficient rats. These studies therefore suggest that VA deficiency, opioid exposure, and HIV infection alone and in combination may potentially alter neuronal metabolic activity and induce cellular stress, resulting in the observed changes in levels of parvalbumin expression. The specific mechanisms that underlie these effects require further study.

Figure 1

Immunoperoxidase staining (a=10x, b=40x magnification) of NeuN+ neurons in frontal cortex.

Figure 2

Quantitative analysis of NeuN+ staining in frontal cortex.

Figure 3

Immunoperoxidase staining for parvalbumin in frontal cortex from (a, b) an untreated WT rat on a normal diet, (c) an untreated WT rat on a VA deficient diet, (d) an untreated TG rat on a normal diet, and (e, f) a morphine-treated TG rat on a VA deficient diet. Magnification: a, c, d, and e = 10x; b and f = 20x.

Figure 4

Quantitative analysis of parvalbumin+ staining in frontal cortex.

Figure 5

Analysis of HIV-1 gene expression in frontal cortex of TG rats on the normal diet or the VA deficient diet treated with placebo or morphine.