Episodic-like memory is sensitive to both Alzheimer's-like pathological accumulation and normal ageing processes in mice

Davis, Kyle; Eacott, Madeline J.; Easton, Alexander; Gigg, John

doi:10.1016/j.bbr.2013.03.009

Cited by 59 publications

(57 citation statements)

References 63 publications

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“…Performance on the task has been shown to be impaired in rodents with damage to the lateral entorhinal cortex (Wilson et al 2013), the first region to be damaged in AD, and the hippocampus (Langston and Woods, 2010). It has also been shown that the triple transgenic murine model of AD show impaired performance on this task at 6 months of age (Davis et al 2013). The current data demonstrate powerful cognitive enhancing effects of both leptin and leptin (116-130) as both groups performed significantly better than controls on the OPC task.…”

Section: Discussionsupporting

confidence: 55%

“…We used the object-place-context (OPC) recognition task which models human episodic memory, the first cognitive process to be compromised in the early stages of AD (Swainson et al 2001). Performance on this task has been shown to be impaired in murine models of AD (Davis et al 2013) and is compromised in animals with lesions of hippocampus (Langston and Wood 2010) and lateral entorhinal cortex (Wilson et al 2013). The task is based on the object recognition paradigm and models the integrated aspect of human episodic memory by exposing rodents to novel combinations of objects, the spatial locations in which they are experienced and the contextual features of the environment (Fig.…”

Section: Leptin (116-130) Enhances Episodic-like Memorymentioning

confidence: 99%

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A Leptin Fragment Mirrors the Cognitive Enhancing and Neuroprotective Actions of Leptin

et al. 2016

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A key pathology of Alzheimer's disease (AD) is amyloid β (Aβ) accumulation that triggers synaptic impairments and neuronal death. Metabolic disruption is common in AD and recent evidence implicates impaired leptin function in AD. Thus the leptin system may be a novel therapeutic target in AD. Indeed, leptin has cognitive enhancing properties and it prevents the aberrant effects of Aβ on hippocampal synaptic function and neuronal viability. However, as leptin is a large peptide, development of smaller leptin-mimetics may be the best therapeutic approach. Thus, we have examined the cognitive enhancing and neuroprotective properties of known bioactive leptin fragments. Here we show that the leptin (116-130) fragment, but not leptin (22-56), mirrored the ability of leptin to promote AMPA receptor trafficking to synapses and facilitate activity-dependent hippocampal synaptic plasticity. Administration of leptin (116-130) also mirrored the cognitive enhancing effects of leptin as it enhanced performance in episodic-like memory tests. Moreover, leptin (116-130) prevented hippocampal synaptic disruption and neuronal cell death in models of amyloid toxicity. These findings establish further the importance of the leptin system as a therapeutic target in AD.

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Section: Discussionsupporting

confidence: 55%

Section: Leptin (116-130) Enhances Episodic-like Memorymentioning

confidence: 99%

A Leptin Fragment Mirrors the Cognitive Enhancing and Neuroprotective Actions of Leptin

et al. 2016

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“…Also story based tests such as the Logical Memory Story A from the Wechsler Memory scale are often used (Weschler, 1987). In rodents the recently described “What-Where-Which” task (WWWhich task), is an episodic-like task, in which animals are tested for the ability to associate an object (what), with its location (where) and its visuospatial context (which occasion) (Davis et al, 2013a, Davis et al, 2013b). Here the context is being used to distinguish a distinct experience or event.…”

Section: Behavioral Studies In Rodentsmentioning

confidence: 99%

“…It has been shown through lesion studies that the ability to successfully associate these three factors, what, where, which occasion, is dependent on an intact hippocampus (Eacott and Norman, 2004, Langston et al, 2010, Langston and Wood, 2010). Also using this task an age dependent decline can be observed in the 3xTg-AD mouse model (Davis et al, 2013a, Davis et al, 2013b). An alternate version of this task distinguishes the episodic event using a time component in place of the visuospatial context, the What-where-when task (WWWhen task), however it is thought that this version of the task does not truly probe episodic memory.…”

Section: Behavioral Studies In Rodentsmentioning

confidence: 99%

Hippocampal neurogenesis: Learning to remember

Lazarov

Hollands

2016

Progress in Neurobiology

217

121

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Alzheimer’s disease, the most prevalent form of dementia in the elderly, is characterized by progressive memory loss and cognitive dysfunction. It has become increasingly clear that while neuronal cell loss in the entorhinal cortex and hippocampus occurs in Alzheimer’s disease, it is preceded by a long period of deficits in the connectivity of the hippocampal formation that contributes to the vulnerability of these circuits. Hippocampal neurogenesis plays a role in the maintenance and function of the dentate gyrus and hippocampal circuitry. This review will examine the evidence suggesting that hippocampal neurogenesis plays a role in cognitive function that is affected in Alzheimer’s disease, will discuss the cognitive assessments used for the detection of Alzheimer’s disease in humans and rodent models of familial Alzheimer’s disease, and their value for unraveling the mechanism underlying the development of cognitive impairments and dementia.

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“…We investigated network hypersynchrony at 3 weeks of age (prior to amyloid plaque deposition, neurofibrillary pathology, and cognitive impairment) in a triple transgenic mouse model of AD (3xTg-AD) that harbors mutated human APP, tau and PS1 genes (Oddo et al, 2003b). The earliest cognitive deficits reported in 3xTg-AD mice are by 2–3 months of age (Davis et al, 2013; Stevens and Brown, 2015). However, most studies show cognitive impairment in 3xTg-AD by ~5 months of age (Oddo et al, 2003b; Billings et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

Early-Onset Network Hyperexcitability in Presymptomatic Alzheimer’s Disease Transgenic Mice Is Suppressed by Passive Immunization with Anti-Human APP/Aβ Antibody and by mGluR5 Blockade

Kazim

Chuang

Zhao

et al. 2017

Front. Aging Neurosci.

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Cortical and hippocampal network hyperexcitability appears to be an early event in Alzheimer’s disease (AD) pathogenesis, and may contribute to memory impairment. It remains unclear if network hyperexcitability precedes memory impairment in mouse models of AD and what are the underlying cellular mechanisms. We thus evaluated seizure susceptibility and hippocampal network hyperexcitability at ~3 weeks of age [prior to amyloid beta (Aβ) plaque deposition, neurofibrillary pathology, and cognitive impairment] in a triple transgenic mouse model of familial AD (3xTg-AD mouse) that harbors mutated human Aβ precursor protein (APP), tau and presenilin 1 (PS1) genes. Audiogenic seizures were elicited in a higher proportion of 3xTg-AD mice compared with wild type (WT) controls. Seizure susceptibility in 3xTg-AD mice was attenuated either by passive immunization with anti-human APP/Aβ antibody (6E10) or by blockade of metabotropic glutamate receptor 5 (mGluR5) with the selective antagonist, 2-methyl-6-(phenylethynyl)pyridine hydrochloride (MPEP). In in vitro hippocampal slices, suppression of synaptic inhibition with the GABAA receptor antagonist, bicuculline, induced prolonged epileptiform (>1.5 s in duration) ictal-like discharges in the CA3 neuronal network in the majority of the slices from 3xTg-AD mice. In contrast, only short epileptiform (<1.5 s in duration) interictal-like discharges were observed following bicuculline application in the CA3 region of WT slices. The ictal-like activity in CA3 region of the hippocampus was significantly reduced in the 6E10-immunized compared to the saline-treated 3xTg-AD mice. MPEP acutely suppressed the ictal-like discharges in 3xTg-AD slices. Remarkably, epileptiform discharge duration positively correlated with intraneuronal human (transgenic) APP/Aβ expression in the CA3 region of the hippocampus. Our data suggest that in a mouse model of familial AD, hypersynchronous network activity underlying seizure susceptibility precedes Aβ plaque pathology and memory impairment. This early-onset network hyperexcitability can be suppressed by passive immunization with an anti-human APP/Aβ antibody and by mGluR5 blockade in 3xTg-AD mice.

show abstract

Episodic-like memory is sensitive to both Alzheimer's-like pathological accumulation and normal ageing processes in mice

Cited by 59 publications

References 63 publications

A Leptin Fragment Mirrors the Cognitive Enhancing and Neuroprotective Actions of Leptin

A Leptin Fragment Mirrors the Cognitive Enhancing and Neuroprotective Actions of Leptin

Hippocampal neurogenesis: Learning to remember

Early-Onset Network Hyperexcitability in Presymptomatic Alzheimer’s Disease Transgenic Mice Is Suppressed by Passive Immunization with Anti-Human APP/Aβ Antibody and by mGluR5 Blockade

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