Age differences in acquisition and retention of one-way avoidance learning in C57BL/6NNia and autoimmune mice

Forster, Michael J.; Popper, Mark D.; Retz, Konrad C.; Lal, Harbans

doi:10.1016/s0163-1047(88)90462-1

Cited by 54 publications

(13 citation statements)

References 31 publications

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“…The active avoidance task required mice to make a preemptive response involving a simple discrimination (running to the correct arm of the maze), to avoid a punishing stimulus (shock to the feet). Previous investigations have indicated an age-dependent decline in performance of C57BL/6 mice in both the "choice" and preemptive running (avoidance) components of this task (Forster et al 1988Forster and Lal 1992;Dubey et al 1996;, and a variety of other studies have reported active avoidance deficits in aging mice and rats, utilizing various testing paradigms (reviewed by Ingram 2001). In particular, it has been noted that older C57BL/6 mice had greater difficulty than young mice in learning a reversal of the correct goal after it had been previously well trained (Dean et al 1981;Forster and Lal 1992;, suggesting an age-related decline in cognitive flexibility.…”

Section: Discussionmentioning

confidence: 99%

Profiling psychomotor and cognitive aging in four-way cross mice

Sumien

Sims

Taylor

et al. 2006

AGE

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In part due to their genetic uniformity and stable characteristics, inbred rodents or their F1 progeny are frequently used to study brain aging. However, it is recognized that focus on a single genotype could lead to generalizations about brain aging that might not apply to the species as a whole, or to the human population. As a potential alternative to uniform genotypes, genetically heterogeneous (HET) mice, produced by a four-way cross, were tested in the current study to determine if they exhibit age-related declines in cognitive and psychomotor function similar to other rodent models of brain aging. Young (4 months) and older (23 months) CB6F1 × C3D2F1 mice were administered a variety of tests for cognitive, psychomotor, and sensory/reflexive capacities. Spontaneous locomotion, rearing, and ability to turn in an alley all decreased with age, as did behavioral measures sensitive to muscle strength, balance, and motor coordination. Although no effect of age was found for either startle response amplitude or reaction time to shock stimuli, the old mice reacted with less force to low intensity auditory stimuli. When tested on a spatial swim maze task, the old mice learned less efficiently, exhibited poorer retention after a 66-h delay, and demonstrated greater difficulty learning a new spatial location. In addition, the older mice were less able to learn the platform location when it was identified by a local visual cue. Because there was a significant correlation between spatial and cued discrimination performance in the old mice, it is possible that age-related spatial maze learning deficits could involve visual or motor impairments. Variation among individuals increased with age for most tests of psychomotor function, as well as for spatial swim performance, suggesting that four-way cross mice may be appropriate models of individualized brain aging. However, the analysis of spatial maze learning deficits in older CB6F1 × C3D2F1 mice may have limited applicability in the study of brain aging, because of a confounding with visually cued performance deficits.

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Section: Discussionmentioning

confidence: 99%

Profiling psychomotor and cognitive aging in four-way cross mice

Sumien

Sims

Taylor

et al. 2006

AGE

Self Cite

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“…Additionally, BXSB and NZB/W F1 mice may have congenital structural abnormalities of the brain (9), potentially confounding structure-function analyses. Both NZB/W F1 and MRL/lpr mice demonstrate neurological deficits (10, 11), though the MRL/lpr model has a greater incidence of neuropsychiatric disease (12). The MRL/lpr has the added benefit of a congenic control (MRL +/+ ), which does not develop disease.…”

Section: Npsle In Human Lupus and Experimental Modelsmentioning

confidence: 99%

Neuropsychiatric Lupus, the Blood Brain Barrier, and the TWEAK/Fn14 Pathway

2013

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Patients with systemic lupus erythematosus (SLE) can experience acute neurological events such as seizures, cerebrovascular accidents, and delirium, psychiatric conditions including depression, anxiety, and psychosis, as well as memory loss and general cognitive decline. Neuropsychiatric SLE (NPSLE) occurs in between 30 and 40% of SLE patients, can constitute the initial patient presentation, and may occur outside the greater context of an SLE flare. Current efforts to elucidate the mechanistic underpinnings of NPSLE are focused on several different and potentially complementary pathways, including thrombosis, brain autoreactive antibodies, and complement deposition. Furthermore, significant effort is dedicated to understanding the contribution of neuroinflammation induced by TNF, IL-1, IL-6, and IFN-γ. More recent studies have pointed to a possible role for the TNF family ligand TWEAK in the pathogenesis of neuropsychiatric disease in human lupus patients, and in a murine model of this disease. The blood brain barrier (BBB) consists of tight junctions between endothelial cells (ECs) and astrocytic projections which regulate paracellular and transcellular flow into the central nervous system (CNS), respectively. Given the privileged environment of the CNS, an important question is whether and how the integrity of the BBB is compromised in NPSLE, and its potential pathogenic role. Evidence of BBB violation in NPSLE includes changes in the albumin quotient (Qalb) between plasma and cerebrospinal fluid, activation of brain ECs, and magnetic resonance imaging. This review summarizes the evidence implicating BBB damage as an important component in NPSLE development, occurring via damage to barrier integrity by environmental triggers such as infection and stress; cerebrovascular ischemia as result of a generally prothrombotic state; and immune mediated EC activation, mediated by antibodies and/or inflammatory cytokines. Additionally, new evidence supporting the role of TWEAK/Fn14 signaling in compromising the integrity of the BBB in lupus will be presented.

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“…The “spontaneous” MRL model has been used for more than two decades (11-14) and proven instrumental in documenting bona fide neurodegeneration of central neurons and cytotoxicity of cerebrospinal fluid (CSF) in SLE-like disease (15;16). In particular, MRL/MpJ-Fas lpr /J (MRL/lpr) and MRL/MpJ (MRL +/+) mice spontaneously develop lupus-like manifestations (e.g., high serum levels of autoantibodies, skin lesions, lymph node and spleen enlargement, renal inflammation), but differ in their onset.…”

Section: Introductionmentioning

confidence: 99%

Effects of prolonged treatment with memantine in the MRL model of central nervous system lupus

Marcinko

Parsons

Lerch

et al. 2012

Clinical & Exp Neuroim

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Objectives Neuropsychiatric manifestations and brain atrophy of unknown etiology are common and severe complications of systemic lupus erythematosus (SLE). An autoantibody that binds to N-methyl-D-aspartate (NMDA) receptor NR2 has been proposed as a key factor in the etiology of central nervous system (CNS) SLE. This hypothesis was supported by evidence suggesting memantine (MEM), an uncompetitive NMDA receptor antagonist, prevents behavioral dysfunction and brain pathology in healthy mice immunized with a peptide similar to an epitope on the NR2 receptor. Given that SLE is a chronic condition, we presently examine the effects of MEM in MRL/lpr mice, which develop behavioral deficits alongside SLE-like disease. Methods A broad behavioral battery and 7-Tesla MRI were used to examine whether prolonged treatment with MEM (~25 mg/kg b.w. in drinking water) prevents CNS involvement in this spontaneous model of SLE. Results Although MEM increased novel object exploration in MRL/lpr mice, it did not show other beneficial, substrain-specific effects. Conversely, MEM was detrimental to spontaneous activity in control MRL +/+ mice and had a negative effect on body mass gain. Similarly, MRI revealed comparable increases in the volume of periventricular structures in MEM-treated groups. Conclusions Sustained exposure to MEM affects body growth, brain morphology, and behavior primarily by pharmacological, and not autoimmunity-dependant mechanisms. Substrain-specific improvement in exploratory behavior of MEM-treated MRL/lpr mice may indicate that the NMDA system is merely a constituent of a complex pathogenenic cascade. However, it was evident that chronic administration of MEM is unable to completely prevent the development of a CNS SLE-like syndrome.

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Age differences in acquisition and retention of one-way avoidance learning in C57BL/6NNia and autoimmune mice

Cited by 54 publications

References 31 publications

Profiling psychomotor and cognitive aging in four-way cross mice

Profiling psychomotor and cognitive aging in four-way cross mice

Neuropsychiatric Lupus, the Blood Brain Barrier, and the TWEAK/Fn14 Pathway

Effects of prolonged treatment with memantine in the MRL model of central nervous system lupus

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