Evaluation of memory, learning ability, and clinical neurologic function in pathogen‐free mice with systemic lupus erythematosus

Vogelweid, Catherine M.; Wright, Dennis C.; Johnson, Jane C.; Hewett, John E.; Walker, Sara E.

doi:10.1002/art.1780370617

Cited by 45 publications

(34 citation statements)

References 28 publications

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“…Similarly to lupus patients, MRL-lpr mice spontaneously develop behavioral dysfunction concerning emotional reactivity, motivated behavior, cognition, as well as pathologic changes in the brain (i.e. degeneration of central neurons) [62,[78][79][80][81][82][83][84][85][86][87]. Experimental studies showed that behavioral deficits parallel high levels of cytokines and autoAb, such as antinuclear Abs, anti-dsDNA, and RF, resulting in large amounts of immune complexes [71].…”

Section: The Mrl-lpr Mouse Modelmentioning

confidence: 97%

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Neuropsychiatric systemic lupus erythematosus and cognitive dysfunction: The MRL-lpr mouse strain as a model

Jeltsch-David

Muller

2014

Autoimmunity Reviews

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Mouse models of autoimmunity, such as (NZB×NZW)F1, MRL/MpJ-Fas(lpr) (MRL-lpr) and BXSB mice, spontaneously develop systemic lupus erythematosus (SLE)-like syndromes with heterogeneity and complexity that characterize human SLE. Despite their inherent limitations, such models have highly contributed to our current understanding of the pathogenesis of SLE as they provide powerful tools to approach the human disease at the genetic, cellular, molecular and environmental levels. They also allow novel treatment strategies to be evaluated in a complex integrated system, a favorable context knowing that very few murine models that adequately mimic human autoimmune diseases exist. As we move forward with more efficient medications to treat lupus patients, certain forms of the disease that requires to be better understood at the mechanistic level emerge. This is the case of neuropsychiatric (NP) events that affect 50-60% at SLE onset or within the first year after SLE diagnosis. Intense research performed at deciphering NP features in lupus mouse models has been undertaken. It is central to develop the first lead molecules aimed at specifically treating NPSLE. Here we discuss how mouse models, and most particularly MRL-lpr female mice, can be used for studying the pathogenesis of NPSLE in an animal setting, what are the NP symptoms that develop, and how they compare with human SLE, and, with a critical view, what are the neurobehavioral tests that are pertinent for evaluating the degree of altered functions and the progresses resulting from potentially active therapeutics.

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Section: The Mrl-lpr Mouse Modelmentioning

confidence: 97%

“…Longer latencies indicate poorer performance. MRL-lpr mice present significant deficits in this test; they are dramatically impaired in their ability to learn the spatial relationships required to guide them to the hidden platform [80,81,86,112].…”

Section: Morris Water Mazementioning

confidence: 99%

Neuropsychiatric systemic lupus erythematosus and cognitive dysfunction: The MRL-lpr mouse strain as a model

Jeltsch-David

Muller

2014

Autoimmunity Reviews

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“…Similar to SLE in humans, an inbred strain of MRL/MpJ-Fas lpr (MRL-lpr) mice develops an accelerated SLE-like condition (Theofilopoulos, 1992) accompanied by various neurological dysfunctions (Hess et al, 1993;Vogelweid et al, 1994), an anxious/depressive-like behavioral state (Sakic et al, 1994), ventricular enlargement (Denenberg et al, 1992), neuronal atrophy, and retarded brain growth (Sakic et al, 2000a;Sakic et al, 1998). Pathological abnormalities are also seen in the choroid plexus, a structure that synthesizes most of the cerebrospinal fluid (CSF) volume (Duprez et al, 2001;Schwartz and Roberts, 1983).…”

Section: Introductionmentioning

confidence: 99%

Proliferating brain cells are a target of neurotoxic CSF in systemic autoimmune disease

Šakić

Kirkham

Ballok

et al. 2005

Journal of Neuroimmunology

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Brain atrophy, neurologic and psychiatric (NP) manifestations are common complications in the systemic autoimmune disease, lupus erythematosus (SLE). Here we show that the cerebrospinal fluid (CSF) from autoimmune MRL-lpr mice and a deceased NP-SLE patient reduce the viability of brain cells which proliferate in vitro. This detrimental effect was accompanied by periventricular neurodegeneration in the brains of autoimmune mice and profound in vivo neurotoxicity when their CSF was administered to the CNS of a rat. Multiple ionic responses with microfluorometry and protein peaks on electropherograms suggest more than one mechanism of cellular demise. Similar to the CSF from diseased MRL-lpr mice, the CSF from a deceased SLE patient with a history of psychosis, memory impairment, and seizures, reduced viability of the C17.2 neural stem cell line. Proposed mechanisms of cytotoxicity involve binding of intrathecally synthesized IgG autoantibodies to target(s) common to different mammalian species and neuronal populations. More importantly, these results indicate that the viability of proliferative neural cells can be compromised in systemic autoimmune disease. Antibody-mediated lesions of germinal layers may impair the regenerative capacity of the brain in NP-SLE and possibly, brain development and function in some forms of CNS disorders in which autoimmune phenomena have been documented. AbbreviationsACA, anti-cardiolipin antibodiesx; Abbreviations, anti-nuclear antibodies; CSF, cerebrospinal fluid; FJB, Fluoro Jade B stain; NP-SLE, neuropsychiatric systemic lupus erythematosus; PBS, phosphate buffered saline

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“…The TLRs trigger innate immunity; because TLR7 binds viral RNA, it may be viral RNA that exacerbates the autoimmune response. Furthermore, because pathogen-free mice also develop lupus (19), the RNA may be produced by endogenous retrovirus.…”

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confidence: 99%

Early onset of autoimmune disease by the retroviral integrase inhibitor raltegravir

Beck-Engeser

Eilat²,

Harrer

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

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Raltegravir is a recently, Food and Drug Administration-approved, small-molecule drug that inhibits retroviral integrase, thereby preventing HIV DNA from inserting itself into the human genome. We report here that the activity profile of raltegravir on the replication of murine leukemia virus is similar to that for HIV, and that the drug specifically affects autoimmune disease in mice, in which endogenous retroelements are suspected to play a role. While NZW and BALB/c mice, which do not succumb to autoimmune disease, are not affected by raltegravir, lupus-prone (NZBx-NZW) F 1 mice die of glomerulonephritis more than a month earlier than untreated mice. Raltegravir-treated NZB mice, which share the H-2 haplotype with BALB/c mice, but which are predisposed to autoimmune hemolytic anemia, develop auto-antibodies to their red blood cells >3 months earlier than untreated mice of the same strain. Because nonautoimmune mice are not affected by raltegravir, we consider off-target effects unlikely and attribute the exacerbation of autoimmunity to the inhibition of retroviral integrase.2-LTR circles ͉ hemolytic anemia ͉ lupus disease ͉ muring leukemia virus ͉ Trex1

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Evaluation of memory, learning ability, and clinical neurologic function in pathogen‐free mice with systemic lupus erythematosus

Cited by 45 publications

References 28 publications

Neuropsychiatric systemic lupus erythematosus and cognitive dysfunction: The MRL-lpr mouse strain as a model

Neuropsychiatric systemic lupus erythematosus and cognitive dysfunction: The MRL-lpr mouse strain as a model

Proliferating brain cells are a target of neurotoxic CSF in systemic autoimmune disease

Early onset of autoimmune disease by the retroviral integrase inhibitor raltegravir

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