Improved psychomotor performance in aged mice fed diet high in antioxidants is associated with reduced ex vivo brain interleukin-6 production

Richwine, Amy F.; Godbout, Jonathan P.; Berg, Brian M.; Chen, J.; Escobar, Javier; Millard, D. K.; Johnson, Rodney W.

doi:10.1016/j.bbi.2004.12.005

Cited by 53 publications

(37 citation statements)

References 31 publications

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“…Because the behavioral deficits evident in HIV-1 infection are largely due to the production of inflammatory molecules in the brain, conditions that facilitate microglial cell activation and production of cytokines, independent of HIV-1 infection, are likely to promote and intensify HAD or other behavioral complications. Therefore, we hypothesized that behavioral deficits induced by HIV-1 gp120 would be greater in aged mice than adults because we previously reported with this model that aging alone induced signs of oxidative stress and production of inflammatory cytokines in the brain [9,17]. A working hypothesis is that cognitive aging is due in part to the emergence of age-associated neuroinflammation [10,25,27].…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, conditions that facilitate microglial cell activation and production of ROS and inflammatory cytokines, independent of HIV-1 infection, are likely to promote and intensify HAD. Interestingly, recent studies indicate that activated microglia, oxidative stress and several inflammatory cytokines are increased in the brains of old but otherwise healthy rodents [9,14,17]. The emergence of signs of inflammation in the brain seems to coincide with indications of cognitive aging [3,17,25].…”

Section: Introductionmentioning

confidence: 99%

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

Abraham

Jang

Godbout

et al. 2008

Neurobiology of Aging

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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-1β 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 dosedependent 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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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

Abraham

Jang

Godbout

et al. 2008

Neurobiology of Aging

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“…This, however, was not the case. One explanation is the low-grade inflammation that is associated with aging Lee et al, 1999Lee et al, , 2000Richwine et al, 2005;Ye and Johnson, 1999). Proinflammatory cytokines degrade proteins and increase the production of positive acute-phase proteins to the detriment of negative acutephase protein such as albumin, which should result in an increase in free TRP.…”

Section: Discussionmentioning

confidence: 99%

Aging exacerbates depressive-like behavior in mice in response to activation of the peripheral innate immune system

Godbout

Moreau

Lestage

et al. 2006

Brain, Behavior, and Immunity

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“…Age is often associated with microglia changes indicative of activation (Frank et al, 2006;McGeer et al, 1987;Perry et al, 1993), and brain inflammation (Kirkwood et al, 2005;Richwine et al, 2005;Ye and Johnson, 1999), and aged mice show greater increases in central inflammatory cytokines compared to adults following both peripheral and central LPS administration (Chen et al, 2008;Godbout et al, 2005;Huang et al, 2007). This exaggerated inflammatory response is accompanied by prolonged sickness behavior and greater deficits in spatial working memory than is seen in adult mice .…”

Section: Introductionmentioning

confidence: 94%

Cognitive and neuroinflammatory consequences of mild repeated stress are exacerbated in aged mice

Buchanan

Sparkman

Chen

et al. 2008

Psychoneuroendocrinology

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104

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SummaryPeripheral immune stimulation as well as certain types of psychological stress increases brain levels of inflammatory cytokines such as interleukin-1β (IL-1β), IL-6 and tumor necrosis factor α (TNFα). We have demonstrated that aged mice show greater increases in central inflammatory cytokines, as well as greater cognitive deficits, compared to adults in response to peripheral lipopolysaccharide (LPS) administration. Because aged mice are typically more sensitive to systemic stressors such as LPS, and certain psychological stressors induce physiological responses similar to those that follow LPS, we hypothesized that aged mice would be more sensitive to the physiological and cognitive effects of mild stress than adult mice. Here, adult (3-5 mo) and aged (22-23 mo) male BALB/c mice were trained in the Morris water maze for 5 days. Mice were then exposed to a mild restraint stress of 30 minutes before being tested in a working memory version of the water maze over a 3 day period. On day 4 mice were stressed and then killed for collection of blood and brain. In a separate group of animals, mice were killed immediately after one, two or three 30 min restraint sessions and blood for peripheral corticosterone and cytokine protein measurement, and brains were dissected for central cytokine mRNA measurement. Stress disrupted spatial working memory in both adult and aged mice but to a much greater extent in the aged mice. In addition, aged mice showed an increase in stress-induced expression of hippocampal IL-1β mRNA and MHC class II protein compared to non-stressed controls while expression in adult mice was unaffected by stress. These data show that aged mice are more sensitive to both the cognitive and inflammatory effects of mild stress than are adult mice and suggest a possible a role for IL-1β.

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Improved psychomotor performance in aged mice fed diet high in antioxidants is associated with reduced ex vivo brain interleukin-6 production

Cited by 53 publications

References 31 publications

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

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

Aging exacerbates depressive-like behavior in mice in response to activation of the peripheral innate immune system

Cognitive and neuroinflammatory consequences of mild repeated stress are exacerbated in aged mice

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