Behavioral impairment of APP(V717F) mice in fear conditioning: is it only cognition?
ABSTRACT Alzheimer's Disease (AD) is a devastating human neurodegenerative disorder associated with progressive deterioration of cognitive abilities. The APP(V717F) mouse, an animal model of AD showing robust overexpression of the human amyloid precursor protein (APP) carrying the mutation 717 V --> F, was also shown to exhibit learning and memory performance deficits. However, AD patients suffer from other abnormalities including altered emotionality. Emotionality has not been analyzed in AD mouse models. Here, motor and posture patterns exhibited by APP(V717F) mice are described in a detailed manner in fear conditioning, a paradigm that allows one to test both mnemonic and emotional characteristics of mice. Our results revealed a complex set of behavioral alterations in APP(V717F) mice in measures of exploratory behavior and fear suggesting that the effects of APP(V717F) overexpression in this mouse model are not limited to cognition and may need to be thoroughly examined in the future in a broad range of behavioral tests.
- SourceAvailable from: Belinda F Bradley
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- "For example, the gerbil neurokinnin receptor is more similar to the human neurokinin receptor than that of rats or mice (Varty et al., 2002a,b; Bridges and Starkey, 2004). In the search for drugs to treat anxiety which do not have the wide ranging and debilitating side effects of the benzodiazepines, neurokinin receptors have been implicated in the aetiology of anxiety (Walsh et al., 1995; Gerlai et al., 2002). The neurokinin-1 receptor shows a different affinity for neurokinin-1 receptor ligands across species, for this reason certain agents that work in humans are less active in rats and mice. "
ABSTRACT: Lavender is a popular treatment for stress and mild anxiety in Europe and the USA. The present study investigated the effects of (Lavandula angustifolia Mill. (Lamiaceae)) lavender odour inhalation over 2 weeks or 24 h periods, on gerbil behaviour in the elevated plus maze in mature male and female gerbils, and compared results with the effects of diazepam (1 mg/kg) i.p. after 30 min and 2-week administration. Traditional measures of open entries showed an increasing trend over the 2 weeks exposure, whereas ethological measures indicative of anxiety; stretch-attend frequency and percentage protected head-dips, were significantly lower. Exploratory behaviour, total head-dip frequency, increased after 24 h lavender and 2 weeks exposure. These results are comparable with diazepam administration. There were sex differences in protected head-dip an ethological indicator of anxiety: females showed a significant decrease in protected head-dips compared to both males and to female controls. In conclusion exposure to lavender odour may have an anxiolytic profile in gerbils similar to that of the anxiolytic diazepam. In addition, prolonged, 2-week lavender odour exposure increased exploratory behaviour in females indicating a further decrease in anxiety in this sex.Journal of Ethnopharmacology 06/2007; 111(3):517-25. DOI:10.1016/j.jep.2006.12.021 · 3.00 Impact Factor
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- "While increasing data suggests an interaction between the two (Phelps, 2006), a third interacting factor, the glucocorticoid stress system, also becomes more apparent. Emotions profoundly influence ongoing and long-term cognitive processes (Acevedo et al., 2006; Blair et al., 2007; Contarino et al., 1999; Dolcos and McCarthy, 2006; Gerlai et al., 2002; Ohl et al., 2003; Steidl et al., 2006; Wall and Messier, 2000). In addition, cognition can also disrupt the response to emotional stimuli (Blair et al., 2007). "
ABSTRACT: Emotionally arousing experiences and stress influence cognitive processes and vice versa. Understanding the relations and interactions between these three systems forms the core of this study. We tested two inbred mouse strains (BALB/c, C57BL/6J; male; 3-month-old) for glucocorticoid stress system markers (expression of MR and GR mRNA and protein in hippocampus, amygdala, and prefrontal cortex; blood plasma corticosterone), used behavioral tasks for emotions and cognitive performance (elevated plus maze, holeboard) to assess the interdependence of these factors. We hypothesize that BALB/c mice have a stress-vulnerable neuroendocrine phenotype and that emotional expressions in BALB/c and C57BL/6J mice will differentially contribute to learning and memory. We applied factor analyses on emotional and cognitive parameters to determine the behavioral structure of BALB/c and C57BL/6J mice. Glucocorticoid stress system markers indeed show that BALB/c mice are more stress-vulnerable than C57BL/6J mice. Moreover, emotional and explorative factors differed between naïve BALB/c and C57BL/6J mice. BALB/c mice display high movement in anxiogenic zones and high risk assessment, while C57BL/6J mice show little movement in anxiogenic zones and display high vertical exploration. Furthermore, BALB/c mice are superior learners, showing learning related behavior which is highly structured and emotionally biased when exposed to a novel or changing situation. In contrast, C57BL/6J mice display a rather "chaotic" behavioral structure during learning in absence of an emotional factor. These results show that stress vulnerability coincides with more emotionality, which drives well orchestrated goal directed behavior to the benefit of cognition. Both phenotypes have their advantage depending on environmental demands.Frontiers in Behavioral Neuroscience 02/2007; 1:8. DOI:10.3389/neuro.08.008.2007 · 3.27 Impact Factor
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- "WM spatial reference memory 3–4, 10, 13, 18 months (non-pro- gressive) Chen et al. (2000) WM serial spatial memory 13, 18 months (progressive) Chen et al. (2000) Cued fear conditioning 11 months Gerlai et al. (2002) Sleep/wake Patterns 3–5 months, 20–26 months (pro- gressive) "
ABSTRACT: Alzheimer's disease (AD) is the most common neurodegenerative affliction of the elderly, presenting with progressive memory loss and dementia and terminating with death. There have been significant advances in understanding the biology and subsequent diagnosis of AD; however, the furious pace of research has not yet translated into a disease-modifying treatment. While scientific inquiry in AD is largely centered on identifying biological players and pathological mechanisms, the day-to-day realities of AD patients and their caregivers revolve around their steady and heartbreaking cognitive decline. In the past decade, AD research has been fundamentally transformed by the development of genetically modified animal models of amyloid-driven neurodegeneration. These important in vivo models not only replicate some of the hallmark pathology of the disease, such as plaque-like amyloid accumulations and astrocytic inflammation, but also some of the cognitive impairments relevant to AD. In this article, we will provide a detailed review of the behavioral and cognitive deficits present in several transgenic mouse models of AD and discuss their functional changes in response to experimental treatments.Genes Brain and Behavior 05/2005; 4(3):173-96. DOI:10.1111/j.1601-183X.2005.00124.x · 3.66 Impact Factor