Neurobehavioral characterization of APP23 transgenic mice with the SHIRPA primary screen
Université de Rouen, Faculté de Médecine et de Pharmacie, INSERM U614, IFRMP23, Bâtiment de Recherche, 76183 Rouen Cedex, France. Behavioural Brain Research
(Impact Factor: 3.03).
03/2005; 157(1):91-8. DOI: 10.1016/j.bbr.2004.06.020
The SHIRPA primary screen comprises 40 measures covering various reflexes and basic sensorimotor functions. This multi-test battery was used to compare non-transgenic controls with APP23 transgenic mice, expressing the 751 isoform of human beta-amyloid precursor protein and characterized by amyloid deposits in parenchyma and vessel walls. The APP23 mice were distinguishable from controls by pathological limb reflexes, myoclonic jumping, seizure activity, and tail malformation. In addition, this mouse model of Alzheimer's disease was also marked by a crooked swimming trajectory. APP23 mice were also of lighter weight and were less inclined to stay immobile during a transfer arousal test. Despite the neurologic signs, APP23 transgenic mice were not deficient in stationary beam, coat-hanger, and rotorod tests, indicating intact motor coordination abilities.
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Available from: Martien J Kas
- "The extended SHIRPA screen used in the present study was a modified version of the standard SHIRPA primary screen that is widely used to assess basic sensorimotoric functions and various reflexes in mice (Lalonde et al., 2005; Rogers et al., 1999). Behavior during the test was recorded with an overhead camera. "
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ABSTRACT: The behavioral characterization of animal models of psychiatric disorders is often based upon independent traits measured at adult age. To model the neurodevelopmental aspects of psychiatric pathogenesis, we introduce a novel approach for a developmental behavioral analysis in mice. C57BL/6 J (C57) mice were used as a reference strain and compared with 129S1/SvImJ (129 Sv), BTBR T+tf/J (BTBR) and A/J (AJ) strains as marker strains for aberrant development. Mice were assessed at pre-adolescence (4 weeks), adolescence (6 weeks), early adulthood (8 weeks) and in adulthood (10–12 weeks) on a series of behavioral tasks measuring general health, neurological reflexes, locomotor activity, anxiety, short- and long term memory and cognitive flexibility. Developmental delays in short-term object memory were associated with either a hypo-reactive profile in 129 Sv mice or a hyper-reactive profile in BTBR mice. Furthermore, BTBR mice showed persistent high levels of repetitive grooming behavior during all developmental stages that was associated with the adult expression of cognitive rigidity. In addition, strain differences in development were observed in puberty onset, touch escape, and body position. These data showed that this longitudinal testing battery provides sufficient behavioral and cognitive resolution during different development stages and offers the opportunity to address the behavioral developmental trajectory in genetic mouse models for neurodevelopmental disorders. Furthermore, the data revealed that the assessment of multiple behavioral and cognitive domains at different developmental stages is critical to determine confounding factors (e.g., impaired motor behavior) that may interfere with the behavioral testing performance in mouse models for brain disorders.
European neuropsychopharmacology: the journal of the European College of Neuropsychopharmacology 06/2014; DOI:10.1016/j.euroneuro.2014.01.013 · 4.37 Impact Factor
Available from: Luciola S Barcelos
- "SHIRPA screening test: The primary SmithKline/Harwell/Imperial College/Royal Hospital/Phenotype Assessment (SHIRPA) screen consists of a wide range of tests, organized into the following five functional categories: neuropsychiatric state (i.e., spontaneous activity, transfer arousal, touch escape, positional passivity, biting, fear, irritability, aggression, vocalizations), motor behavior (i.e., body position, tremor, locomotor activity, pelvic elevation, gait, tail elevation, trunk curl, limb grasping, wire maneuver, negative geotaxis), reflex and sensory function (i.e., startle response, visual placing, pinna reflex, corneal reflex, toe pinch, righting reflex), autonomic function (i.e., respiratory rate, defecation, urination, palpebral closure, piloerection, skin color, heart rate, lacrimation, salivation, body temperature) and muscle tone and strength (i.e., grip strength, body tone, limb tone, abdominal tone). The SHIRPA provides a basic behavioral and functional profile through the observational assessment of individual performance (14). All measures were performed in a Plexiglas square arena (40 cm × 40 cm × 30 cm). "
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ABSTRACT: Ischemic stroke may result from transient or permanent reductions of regional cerebral blood flow. Polymorphonuclear neutrophils have been described as the earliest inflammatory cells to arrive in ischemic tissue. CXCR1/2 receptors are involved in the recruitment of these cells. However, the contribution of these chemokine receptors during transient brain ischemia in mice remains poorly understood. In this work, we investigated the effects of reparixin, an allosteric antagonist of CXCR1/2 receptors, in a model of middle cerebral artery occlusion and reperfusion in mice.
C57BL/6J male mice treated with reparixin or vehicle were subjected to a middle cerebral artery occlusion procedure 1 h after the treatment. Ninety minutes after ischemia induction, the monofilament that prevented blood flow was removed. Twenty-four hours after the reperfusion procedure, behavioral changes, including motor signs, were analyzed with the SmithKline/Harwell/lmperial College/Royal Hospital/Phenotype Assessment (SHIRPA) battery. The animals were sacrificed, and brain tissue was removed for histological and biochemical analyses. Histological sections were stained with hematoxylin and eosin, neutrophil infiltration was estimated by myeloperoxidase activity and the inflammatory cytokine IL-iβ was measured by ELISA.
Pre-treatment with reparixin reduced the motor deficits observed in this model of ischemia and reperfusion. Myeloperoxidase activity and IL-iβ were reduced in the reparixin-treated group. Histological analysis revealed that ischemic injury was also attenuated by reparixin pre-treatment.
Our results suggest that the blockade of the CXCR1/2 receptors by reparixin promotes neuroprotective effects by reducing the levels of polymorphonuclear infiltration in the brain and the tissue damage associated with middle cerebral artery occlusion and reperfusion.
Clinics (São Paulo, Brazil) 03/2013; 68(3):391-4. DOI:10.6061/clinics/2013(03)OA17 · 1.19 Impact Factor
Available from: Mingke Song
- "The screen test was performed to identify gross phenotypic and behavioural characteristics. We followed similar protocol procedures as described online by the MRC Harwell centre for mouse genetics (http://empress.har.mrc.ac.uk/; Lalonde et al. 2005). Mice were placed inside a glass beaker and inspected for the following phenotypes: body position (0 = inactive, 1 = active, 2 = excessively active); tremor (0 = absent, 1 = present); palpebral closure (0 = eyes open, 1 = eyes closed); coat appearance (0 = tidy, well groomed, 1 = irregular); whiskers (0 = present, 1 = absent); and defecation (0 = present, 1 = absent). "
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ABSTRACT: Since the discovery of the glutamate NMDA receptor subunit 3A (GluN3A), the functional role of this unique inhibitory subunit has been largely obscure. GluN3A expression is high in the neonatal brain but declines to a low level in the adult brain; it is thus commonly believed that GluN3A does not have a major functional impact in adulthood. Using wild-type (WT) and GluN3A knockout (KO) mice, we show here that deletion of GluN3A affected multiple behavioural functions in adult animals. GluN3A KO mice showed impaired locomotor activity on a variety of motor function tests, and increased sensitivity to acute and sub-acute inflammatory pain. GluN3A KO mice also showed enhanced recognition and spatial learning and memory functions. Hippocampal slices from juvenile and adult GluN3A KO mice showed greater long-term potentiation (LTP) compared with WT slices. GluN3A deletion resulted in increased expression of Ca2+/calmodulin-dependent kinase II (CaMKII) in the forebrain, and the phosphorylated CaMKII level upon LTP induction was significantly higher in the GluN3A KO hippocampus compared with WT controls. CaMKII inhibition abrogated the enhanced LTP in GluN3A KO slices. These data reveal for the first time that the presence of GluN3A may have profound impacts on several functional/behavioural activities in adult animals, and could be a therapeutic target for neurological disorders associated with NMDA receptor functions.
The Journal of Physiology 01/2013; 591(1). DOI:10.1113/jphysiol.2012.239251 · 5.04 Impact Factor
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