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Comparative Study
. 2008 Apr;29(4):614-21.
doi: 10.1016/j.neurobiolaging.2006.11.002. Epub 2006 Dec 15.

Aging sensitizes mice to behavioral deficits induced by central HIV-1 gp120

J Abraham  1 , S Jang, J P Godbout, J Chen, K W Kelley, R Dantzer, R W Johnson
Affiliations
Comparative Study

Aging sensitizes mice to behavioral deficits induced by central HIV-1 gp120

J Abraham et al. Neurobiol Aging. 2008 Apr.

Abstract

The number of older adults with HIV-1 disease is increasing but little is known about how age influences behavioral deficits associated with HIV-1 infection. The purpose of this study was to determine in a murine model if aging influenced sickness behavior following central injection of HIV-1 gp120. In initial studies, behavioral deficits induced by acute and repeated intracerebroventricular (ICV) injection of gp120 were greater in aged mice than in adults. Furthermore, repeated ICV injection of gp120 increased hippocampal levels of IL-1 beta and IL-6 mRNA in aged mice but not in adults. To determine if IL-6, which is elevated in aged brain, affects expression of the gp120-binding target, CCR5, microglia (BV-2 cell line) were incubated with increasing concentrations of IL-6. Cell surface expression of CCR5 was increased by IL-6 in a dose-dependent manner. Additionally, IL-6 increased gp120-dependent chemotaxis. These results suggest that aging increases the sensitivity of mice to behavioral deficits caused by ICV gp120, perhaps by increasing expression of CCR5 and augmenting production of cytokines.

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Figures

Figure 1
Figure 1. Aging prolonged gp120-induced deficits in social behavior and locomotor activity
Adult and aged mice were injected i.c.v. with either saline or gp120 (100ng) and (A) social behavior and (B) locomotor activity were measured at 0, 2, 4, 8, and 24 hours after injection. Graphs are means ± SEM (n=8-9). Means with * are significantly different (p<0.05).
Figure 2
Figure 2. Aging further depressed deficits in locomotor activity caused by chronic administration of gp120
Adult (A) and aged (B) mice received a daily injection of saline or gp120 (100ng) for 5 consecutive days. Locomotor activity was assessed each day just prior to injection. Graphs are means ± SEM (n=8-10). Means with * are significantly different (p<0.05).
Figure 3
Figure 3. Aging increased hippocampal IL-6 and IL-1β mRNA
Adult (A) and aged (B) mice received a daily injection of saline or gp120 (100ng) for 5 consecutive days. 24 h after the last injection, hippocampal tissue was collected and cytokine mRNA were quantified by real-time PCR. Bars represent means ± SEM (n=8-10). Means with * are significantly different (p<0.05).
Figure 4
Figure 4. Expression of CCR5 on microglia is induced by IL-6
Exposure to IL-6 increased the number of BV-2 cells expressing CCR5 (A). Treatment of BV-2 cells with IL-6 for 24 h increased CCR5 cell surface expression in a dose-dependent manner (B). Bars represent means ± SEM. Means with different letters (a, b, or c) are significantly different (p<0.05) from each other.
Figure 5
Figure 5. Microglial cell chemotaxis toward macrophage-tropic gp120 is enhanced by IL-6
Pre-treatment with IL-6 increased the chemotactic response of BV-2 cells to RANTES (A) and M-tropic gp120 (C). Pretreatment with IL-6 increased the number of migrating BV-2 cells in a dose-dependent manner when either RANTES (B) or M-tropic gp120 (D) were used as chemoattractants. Bars represent means ± SEM. Means with different letters (a, b, c, d, or e) are significantly different (p<0.05) from each other.
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References

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