Mouse Behavioural Studies and What They Can Teach Us about Prion Diseases

Cunningham, Colm

doi:10.1007/0-387-23923-5_5

Cited by 5 publications

(12 citation statements)

References 62 publications

(77 reference statements)

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“…The first sign of hippocampal-dependent sickness behavior was observed in burrowing activity tests at 14th wpi, while locomotor changes or exploratory activity on open field and muscle strength changed later in the disease (17th wpi) and these results are in line with previous reports [13, 17]. Our results show that the ME7 injection in the dorsal hippocampus reproduced the temporal course of the disease as previously described elsewhere [13].…”

Section: Discussionsupporting

confidence: 93%

“…The open field test, which evaluates the pattern of spontaneous exploratory activity, reproduced previous results [17]. However, in this study the hyperactivity, which appeared in other studies around the 12th wpi, only became apparent at 15th wpi.…”

Section: Discussionsupporting

confidence: 87%

“…This result is consistent with previous studies that demonstrated, regardless of the route of inoculation of the prion agent, the hippocampus is one of the main target of chronic neurodegeneration associated with the disease [22] and the burrowing test is sensitive and specific to hippocampal damage [23, 24]. The temporal identification of behavioral changes in the course of prion disease varies from one study to another, but it is known that changes in spontaneous behavior, such as decrease in burrowing activity and hyperactivity, occur before reduction in the performances on behavioral tests that require strength and motor coordination [17]. Our findings are in line with these descriptions.…”

Section: Discussionmentioning

confidence: 99%

“…The dorsal hippocampus was target used for the injection site. The subsequent hippocampal neurodegeneration gives rise to a defined sequence of behavioral alterations [17] that could be readily detected.…”

Section: Methodsmentioning

confidence: 99%

“…Inflammatory preexistent conditions such as those associated with chronic neurodegenerative diseases in humans and mice seem to be aggravated by both peripheral and central infections [14–17]. Indeed, cognitive deficits of patients with Alzheimer's disease is further increased after a systemic infection and this is preceded by an increase in interleukin 1 β [14] and mouse prion disease shows more intense neuropathological features and faster disease progression after systemic and central endotoxin challenges [15].…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

Virus Infections on Prion Diseased Mice Exacerbate Inflammatory Microglial Response

Lins

Mourão

Trévia

et al. 2016

Oxidative Medicine and Cellular Longevity

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We investigated possible interaction between an arbovirus infection and the ME7 induced mice prion disease. C57BL/6, females, 6-week-old, were submitted to a bilateral intrahippocampal injection of ME7 prion strain (ME7) or normal brain homogenate (NBH). After injections, animals were organized into two groups: NBH (n = 26) and ME7 (n = 29). At 15th week after injections (wpi), animals were challenged intranasally with a suspension of Piry arbovirus 0.001% or with NBH. Behavioral changes in ME7 animals appeared in burrowing activity at 14 wpi. Hyperactivity on open field test, errors on rod bridge, and time reduction in inverted screen were detected at 15th, 19th, and 20th wpi respectively. Burrowing was more sensitive to earlier hippocampus dysfunction. However, Piry-infection did not significantly affect the already ongoing burrowing decline in the ME7-treated mice. After behavioral tests, brains were processed for IBA1, protease-resistant form of PrP, and Piry virus antigens. Although virus infection in isolation did not change the number of microglia in CA1, virus infection in prion diseased mice (at 17th wpi) induced changes in number and morphology of microglia in a laminar-dependent way. We suggest that virus infection exacerbates microglial inflammatory response to a greater degree in prion-infected mice, and this is not necessarily correlated with hippocampal-dependent behavioral deficits.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionsupporting

confidence: 87%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Virus Infections on Prion Diseased Mice Exacerbate Inflammatory Microglial Response

Lins

Mourão

Trévia

et al. 2016

Oxidative Medicine and Cellular Longevity

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Age and Environment Influences on Mouse Prion Disease Progression: Behavioral Changes and Morphometry and Stereology of Hippocampal Astrocytes

Bento-Torres

Sobral

Reis

et al. 2017

Oxidative Medicine and Cellular Longevity

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Because enriched environment (EE) and exercise increase and aging decreases immune response, we hypothesized that environmental enrichment and aging will, respectively, delay and increase prion disease progression. Mice dorsal striatum received bilateral stereotaxic intracerebral injections of normal or ME7 prion infected mouse brain homogenates. After behavior analysis, animals were euthanized and their brains processed for astrocyte GFAP immunolabeling. Our analysis related to the environmental influence are limited to young adult mice, whereas age influence refers to aged mice raised on standard cages. Burrowing activity began to reduce in ME7-SE two weeks before ME7-EE, while no changes were apparent in ME7 aged mice (ME7-A). Object placement recognition was impaired in ME7-SE, NBH-A, and ME7-A but normal in all other groups. Object identity recognition was impaired in ME7-A. Cluster analysis revealed two morphological families of astrocytes in NBH-SE animals, three in NBH-A and ME7-A, and four in NBH-EE, ME7-SE, and ME7-EE. As compared with control groups, astrocytes from DG and CA3 prion-diseased animals show significant numerical and morphological differences and environmental enrichment did not reverse these changes but induced different morphological changes in GFAP+ hippocampal astroglia. We suggest that environmental enrichment and aging delayed hippocampal-dependent behavioral and neuropathological signs of disease progression.

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Influence of Enriched Environment on Viral Encephalitis Outcomes: Behavioral and Neuropathological Changes in Albino Swiss Mice

et al. 2011

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An enriched environment has previously been described as enhancing natural killer cell activity of recognizing and killing virally infected cells. However, the effects of environmental enrichment on behavioral changes in relation to virus clearance and the neuropathology of encephalitis have not been studied in detail. We tested the hypothesis that environmental enrichment leads to less CNS neuroinvasion and/or more rapid viral clearance in association with T cells without neuronal damage. Stereology-based estimates of activated microglia perineuronal nets and neurons in CA3 were correlated with behavioral changes in the Piry rhabdovirus model of encephalitis in the albino Swiss mouse. Two-month-old female mice maintained in impoverished (IE) or enriched environments (EE) for 3 months were behaviorally tested. After the tests, an equal volume of Piry virus (IEPy, EEPy)-infected or normal brain homogenates were nasally instilled. Eight days post-instillation (dpi), when behavioral changes became apparent, brains were fixed and processed to detect viral antigens, activated microglia, perineuronal nets, and T lymphocytes by immuno- or histochemical reactions. At 20 or 40 dpi, the remaining animals were behaviorally tested and processed for the same markers. In IEPy mice, burrowing activity decreased and recovered earlier (8–10 dpi) than open field (20–40 dpi) but remained unaltered in the EEPy group. EEPy mice presented higher T-cell infiltration, less CNS cell infection by the virus and/or faster virus clearance, less microgliosis, and less damage to the extracellular matrix than IEPy. In both EEPy and IEPy animals, CA3 neuronal number remained unaltered. The results suggest that an enriched environment promotes a more effective immune response to clear CNS virus and not at the cost of CNS damage.

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Mouse Behavioural Studies and What They Can Teach Us about Prion Diseases

Cited by 5 publications

References 62 publications

Virus Infections on Prion Diseased Mice Exacerbate Inflammatory Microglial Response

Virus Infections on Prion Diseased Mice Exacerbate Inflammatory Microglial Response

Age and Environment Influences on Mouse Prion Disease Progression: Behavioral Changes and Morphometry and Stereology of Hippocampal Astrocytes

Influence of Enriched Environment on Viral Encephalitis Outcomes: Behavioral and Neuropathological Changes in Albino Swiss Mice

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