APP transgenic mice for modelling behavioural and psychological symptoms of dementia (BPSD)

Lalonde, Robert; Fukuchi, Ken-ichiro; Strazielle, C.

doi:10.1016/j.neubiorev.2012.02.011

Cited by 57 publications

(49 citation statements)

References 328 publications

(551 reference statements)

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“…These symptoms may age-dependently occur in transgenic mice (Hsiao et al, 1996;Moechars et al, 1999;Chen et al, 2000). It has been reported that the APP transgenic mice are valuable tools to develop new drugs for dementia and BPSD (Lalonde et al, 2012). The present data indicate that a single injection of Aβ1-42 (500 pmol/mouse) into the lateral ventricle of individually housing adult mice irreversibly induces cognitive decline and BPSD-like symptoms in a few weeks and may be a protocol to prepare a model for BPSD with dementia.…”

Section: Discussionmentioning

confidence: 49%

Involvement of hippocampal excitability in amyloid β-induced behavioral and psychological symptoms of dementia

et al. 2016

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-In patients with Alzheimer's disease, in addition to the core symptoms, i.e., cognitive dysfunction, behavioral and psychological symptoms of dementia (BPSD) such as aggression, anxiety, and hallucinations are known to occur frequently. Because various environmental factors influence the onset and progression of Alzheimer's disease, in the present study, BPSD-like behavioral abnormality of Amyloid β (Aβ)1-42-injected mice was assessed under social isolation, which induces behavioral abnormality. Aβ protein (500 pmol) was injected into the lateral ventricle of mice, which were individually housed. Two and three weeks after injection into adult mice, the rate of mice that exhibited aggressive behavior, i.e., biting attacks and wrestling, to the total mice, was markedly increased by Aβ injection. Aβ-injected adult mice also showed anxiety-like behavior, in addition to cognitive decline. Serum corticosterone level was markedly increased by Aβ injection. When excitability of hippocampal neurons was checked using hippocampal slices, KCl-induced presynaptic activity was enhanced in hippocampal slices prepared from Aβ-injected mice. These results suggest that social isolation housing of Aβ1-42-injected adult mice induces BPSD-like behavioral abnormality in addition to cognitive decline. It is likely that behavioral abnormality of Aβ1-42-injected adult mice is associated with excitability of hippocampal glutamatergic neurons, which is associated with the elevated corticosterone level.

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Section: Discussionmentioning

confidence: 49%

Involvement of hippocampal excitability in amyloid β-induced behavioral and psychological symptoms of dementia

et al. 2016

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“…OFT perimeter vertical counts also demonstrated a significant age × genotype interaction, as counts increased with age in APP/PS1/KALRN(+/+) mice while declining in KALRN(+/+), although these changes were not independently significant. Spontaneous Alternation percent correct, which could be seen as a measure of apathetic or perseverative behavior (Lalonde et al, 2012), did not differ between APP/PS1/KALRN(+/+) and KALRN(+/+) mice (data not shown).…”

Section: Resultsmentioning

confidence: 95%

“…A recent comprehensive review concluded that despite some conflicting findings, increased hyperactivity in the open field test with age was the most common pattern in mice transgenic for the APPswe mutation, including in APPswe/PSEN1dE9 mice, suggesting a relationship to accumulation of pathology (Lalonde et al, 2012). APP transgenic mice strains were more variable in demonstrating decreased, increased, or unchanged anxiety/inhibition (Lalonde et al, 2012), although several studies have reported APPswe/PSEN1dE9 mice to evidence disinhibition/reduced anxiety (Dumont et al, 2004; Lalonde et al, 2005; Reiserer et al, 2007). …”

Section: Introductionmentioning

confidence: 99%

Kalirin reduction rescues psychosis-associated behavioral deficits in APPswe/PSEN1dE9 transgenic mice

Krivinko

Erickson

Abrahamson

et al. 2017

Neurobiology of Aging

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Psychosis in Alzheimer disease (AD+P) represents a distinct clinical and neurobiological AD phenotype, and is associated with more rapid cognitive decline, higher rates of abnormal behaviors, and increased caregiver burden compared to AD without psychosis. On a molecular level, AD+P is associated with greater reductions in the protein kalirin, a guanine exchange factor which has also been linked to the psychotic disease, schizophrenia. In this study, we sought to determine the molecular and behavioral consequences of kalirin reduction in APPswe/PSEN1dE9 mice. We evaluated mice with and without kalirin reduction during tasks measuring psychosis-associated behaviors and spatial memory. We found that kalirin reduction in APPswe/PSEN1dE9 mice significantly attenuated psychosis-associated behavior at 12 months of age without changing spatial memory performance. The 12 month old APPswe/PSEN1dE9 mice with reduced kalirin levels also had increased levels of the active, phosphorylated form of p21 protein (Cdc42/Rac)-activated kinases (PAKs), which function in signaling pathways for maintenance of dendritic spine density, morphology, and function.

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“…Although several reviews of murine Alzheimer models have appeared (Van Leuven, 2000; Ashe, 2001; Morgan, 2003; Sant’ Angelo et al, 2003; German and Eisch, 2004; Mineur et al, 2005; Spires and Hyman, 2005; McGowan et al, 2006; Gimenez-Llort et al, 2007; Duyckaerts et al, 2008; Howlett and Richardson, 2009; Kokjohn et al, 2009; Ashe and Zahs, 2010; Wirths and Bayer, 2010; Scearce-Levie, 2011; Lalonde et al, 2012), the authors mostly describe the effects of accumulating Aβ concentrations on synaptic activity or learning abilities in various spatial and non-spatial tasks. We present in-depth task-by-task effects of APP transgenesis on survival and basic neurologic functions regarding pathological reflexes, myoclonus, and epilepsy.…”

Section: Neurologic Symptoms and Survival Rates In App Micementioning

confidence: 99%

Neurologic and motor dysfunctions in APP transgenic mice

Lalonde

Fukuchi

Strazielle

2012

Reviews in the Neurosciences

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The discovery of gene mutations underlying autosomal dominant Alzheimer’s disease has enabled researchers to reproduce several hallmarks of this disorder in transgenic mice, notably the formation of Aβ plaques in brain and cognitive deficits. APP transgenic mutants have also been investigated with respect to survival rates, neurologic functions, and motor coordination, which are all susceptible to alteration in Alzheimer dementia. Several transgenic lines expressing human mutated or wild-type APP had higher mortality rates than non-transgenic controls with or without the presence of Aβ plaques. Mortality rates were also elevated in APP transgenic mice with vascular amyloid accumulation, thereby implicating cerebrovascular factors in the precocious death observed in all APP transgenic models. In addition, myoclonic jumping has been described in APP mutants, together with seizure activity, abnormal limb-flexion and paw-clasping reflexes, and motor coordination deficits. The neurologic signs resemble the myoclonic movements, epileptic seizures, pathological reflexes, and gait problems observed in late-stage Alzheimer’s disease.

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APP transgenic mice for modelling behavioural and psychological symptoms of dementia (BPSD)

Cited by 57 publications

References 328 publications

Involvement of hippocampal excitability in amyloid β-induced behavioral and psychological symptoms of dementia

Involvement of hippocampal excitability in amyloid β-induced behavioral and psychological symptoms of dementia

Kalirin reduction rescues psychosis-associated behavioral deficits in APPswe/PSEN1dE9 transgenic mice

Neurologic and motor dysfunctions in APP transgenic mice

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