Spatial learning impairment in a murine model of AIDS

Sei, Yoshitatsu; Arora, Prince K.; Skolnick, Phil; Paul, Ian A.

doi:10.1096/fasebj.6.11.1644264

Cited by 56 publications

(38 citation statements)

References 20 publications

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“…Movement patterns were very similar to those previously described by Sei et al (1992). During the first two trials thigmatactic movement was dominant.…”

Section: Movement Patternssupporting

confidence: 85%

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Effects of chronic administration of adenosine A1 receptor agonist and antagonist on spatial learning and memory

Lubitz

Paul

Bartus

et al. 1993

European Journal of Pharmacology

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Spatial memory acquisition in Morris water maze was tested in C57BL/6 mice. Animals were injected once daily with different doses of either N 6 -cyclopentyladenosine (CPA) or 8-cyclopentyl-1,3-dipropylxanthine (CPX). Drugs were administered for 9 days either concurrently with water maze testing (drugs injected 1 h after each trial), or prior to the entire block of trials. In the latter case, 1 day without injections preceded water maze experiments. Chronic administration of CPA resulted in a significant, dose-dependent reduction of target latencies, rapid development of spatial preference, and the absence of animals unable to perform the task. CPX treated animals did not show significant performance changes, and failed to develop spatial preference. Locomotor disturbances were not the cause of the observed effects. Our results indicate that chronic treatment with agents acting at adenosine A 1 receptors results in behavioral effects that are significantly different from those observed following their acute administration. Therefore, particular caution is required in development of adenosine-based strategies targeted at neurodegenerative or cognitive disorders in which chronic treatment is advocated.

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“…Movement patterns were very similar to those previously described by Sei et al (1992). During the first two trials thigmatactic movement was dominant.…”

Section: Movement Patternssupporting

confidence: 85%

“…Based on previous experiments of Sei et al (1992), the performance of animals in reaching the target (target latency) was defined as 'good' (≤40 s), 'average' (41-90 s) and 'poor' (> 90 s). Animals were trained once daily beginning at 3 p.m.…”

Section: Trainingmentioning

confidence: 99%

Effects of chronic administration of adenosine A1 receptor agonist and antagonist on spatial learning and memory

Lubitz

Paul

Bartus

et al. 1993

European Journal of Pharmacology

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“…In mice with MAIDS, pancreatic lesions of the exocrine system with a predominance of infiltrating Th2 cells have been described (28); moreover, CNS damage and cognitive deficits develop concurrently with the immunodeficiency (29)(30)(31). Hence, the thiol content in the pancreas and brain was also analyzed.…”

Section: Gsh and Cysteine Levels In Organs Of Lp-bm5-infected Micementioning

confidence: 99%

“…Moreover, it has been reported that LP-BM5 infection is accompanied by a pancreatitis-like injury (28) and by central nervous system (CNS) damage (29)(30)(31). Hence, to investigate whether the thiol content could play a role in the alterations of these organs, GSH and cysteine levels were also measured in the pancreas and brain.…”

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confidence: 99%

Glutathione Depletion Is Linked with Th2 Polarization in Mice with a Retrovirus-Induced Immunodeficiency Syndrome, Murine AIDS: Role of Proglutathione Molecules as Immunotherapeutics

Brundu

Palma

Picceri

et al. 2016

J Virol

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Injection of the LP-BM5 murine leukemia virus into mice causes murine AIDS, a disease characterized by many dysfunctions of immunocompetent cells. To establish whether the disease is characterized by glutathione imbalance, reduced glutathione (GSH) and cysteine were quantified in different organs. A marked redox imbalance, consisting of GSH and/or cysteine depletion, was found in the lymphoid organs, such as the spleen and lymph nodes. Moreover, a significant decrease in cysteine and GSH levels in the pancreas and brain, respectively, was measured at 5 weeks postinfection. The Th2 immune response was predominant at all times investigated, as revealed by the expression of Th1/Th2 cytokines. Furthermore, investigation of the activation status of peritoneal macrophages showed that the expression of genetic markers of alternative activation, namely, Fizz1, Ym1, and Arginase1, was induced. Conversely, expression of inducible nitric oxide synthase, a marker of classical activation of macrophages, was detected only when Th1 cytokines were expressed at high levels. In vitro studies revealed that during the very early phases of infection, GSH depletion and the downregulation of interleukin-12 (IL-12) p40 mRNA were correlated with the dose of LP-BM5 used to infect the macrophages. Treatment of LP-BM5-infected mice with N-(N-acetyl-L-cysteinyl)-S-acetylcysteamine (I-152),an N-acetyl-cysteine supplier, restored GSH/cysteine levels in the organs, reduced the expression of alternatively activated macrophage markers, and increased the level of gamma interferon production, while it decreased the levels of Th2 cytokines, such as IL-4 and IL-5. Our findings thus establish a link between GSH deficiency and Th1/Th2 disequilibrium in LP-BM5 infection and indicate that I-152 can be used to restore the GSH level and a balanced Th1/Th2 response in infected mice. IMPORTANCEThe first report of an association between Th2 polarization and alteration of the redox state in LP-BM5 infection is presented. Moreover, it provides evidence that LP-BM5 infection causes a decrease in the thiol content of peritoneal macrophages, which can influence IL-12 production. The restoration of GSH levels by GSH-replenishing molecules can represent a new therapeutic avenue to fight this retroviral infection, as it reestablishes the Th1/Th2 balance. Immunotherapy based on the use of pro-GSH molecules would permit LP-BM5 infection and probably all those viral infections characterized by GSH deficiency and a Th1/ Th2 imbalance to be more effectively combated. Infection with the LP-BM5 murine leukemia virus causes a profound and broad immunodeficiency in susceptible mouse strains, such as C57BL/6 (B6) mice. This disease is known as murine AIDS (MAIDS) and is characterized by early polyclonal T-and B-cell activation, splenomegaly, lymphadenopathy, hypergammaglobulinemia, decreased T-and B-cell responses, increased susceptibility to opportunistic pathogens, and the development of terminal B-cell lymphomas and neurological dysfunctions (1-4). MAIDS is charact...

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“…The open-field water maze or 'Morris water maze' has been used extensively to examine behavioural, neural and physiological substrates of spatial mapping and learning in rodents (Morris, 1984). Several studies, utilising a range of infectious agents including parasitic nematodes (Kavaliers and Colwell, 1995;Braithwaite et al, 1998) and immune deficiency virus (Sei et al, 1992) (Gundra et al, 2011). The wide availability of knockout mice would also allow for direct correlation between specific cytokines and behavioural alterations.…”

Section: Going Forwardmentioning

confidence: 99%

The significance of cerebral toxocariasis: a model system for exploring the link between brain involvement, behaviour and the immune response

Holland

Hamilton

2013

Journal of Experimental Biology

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SummaryToxocara canis is a parasitic nematode that infects canines worldwide, and as a consequence of the widespread environmental dissemination of its ova in host faeces, other abnormal hosts including mice and humans are exposed to infection. In such abnormal or paratenic hosts, the immature third-stage larvae undergo a somatic migration through the organs of the body but fail to reach maturity as adult worms in the intestine. The presence of the migrating larvae contributes to pathology that is dependent upon the intensity of infection and the location of the larvae. A phenomenon of potential public health significance in humans and of ecological significance in mice is that T. canis larvae exhibit neurotrophic behaviour, which results in a greater concentration of parasites in the brain, as infection progresses. Toxocara larval burdens vary between individual outbred mice receiving the same inocula, suggesting a role for immunity in the establishment of cerebral infection. Although the systemic immune response to T. canis has been widely reported, the immune response in the brain has received little attention. Differential cytokine expression and other brain injury-associated biomarkers have been observed in infected versus uninfected outbred and inbred mice. Preliminary data have also suggested a possible link between significant memory impairment and cytokine production associated with T. canis infection. Mice provide a useful, replicable animal model with significant applicability and ease of manipulation. Understanding the cerebral host-parasite relationship may shed some light on the cryptic symptoms of human infection where patients often present with other CNS disorders such as epilepsy and mental retardation.

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Spatial learning impairment in a murine model of AIDS

Cited by 56 publications

References 20 publications

Effects of chronic administration of adenosine A1 receptor agonist and antagonist on spatial learning and memory

Effects of chronic administration of adenosine A1 receptor agonist and antagonist on spatial learning and memory

Glutathione Depletion Is Linked with Th2 Polarization in Mice with a Retrovirus-Induced Immunodeficiency Syndrome, Murine AIDS: Role of Proglutathione Molecules as Immunotherapeutics

The significance of cerebral toxocariasis: a model system for exploring the link between brain involvement, behaviour and the immune response

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