morris-water-maze-test-optimization-for-mouse-strain-testing

Morris Water Maze Test: Optimization for Mouse Strain and Testing Environment

 The Morris water maze (MWM) is a commonly used task to assess hippocampal-dependent spatial learning and memory in transgenic mouse models of disease, ...

West Virginia University

The Cognistat is a widely used screening instrument for the assessment of higher cerebral functioning. This study investigated the effects of gender and age on a specific item from the metric sequence of the Cognistat Judgment subtest. Participants consisted of 110 cognitively intact volunteers (45 males, 65 females). Results showed that females responded with 1-point answers, as defined by the manual, significantly more often than those who responded with a manual-defined 2-point response. Males responded with a 2-point answer with a significantly greater frequency than they responded with 1-point responses. The data indicate that a gender correction for females should be made to the Judgment subtest of the Cognistat.

Correcting for gender on the Cognistat Judgment subtest.

Transgenic mice expressing mutations in tau have yielded essential discoveries for Alzheimer's disease. One of the most commonly used tau mouse models is the tet-off Tg(tauP301L)4510 model that expresses P301L human tau driven by the calcium-calmodulin kinase IIα (CaMKIIα) promoter system. Tau expression in this model is regulatable, allowing for suppression of mutant tau expression until adulthood and prevention of possible developmental alterations resulting from P301L tau expression during development. Here, we compared the effect and sample sizes needed for three learning and memory tasks in mice with adult-onset P301L tau expression. Our findings indicate that the Incremental Repeated Acquisition (IRA) and trace fear conditioning tasks, neither of which have previously been published with these mice, were highly sensitive to P301L tau expression, whereas the Morris water maze, the most commonly used task with this model, was the least sensitive. Memory deficits were observed at a time when tau pathology was subtle and prior to readily detectable neuronal loss. Thus, we provide essential information (effect and sample sizes needed) for establishing experimental designs at a time point when memory deficits are likely to go undetected if inadequate sample sizes are used. Our work also suggests the tet-off Tg4510 model provides a way to avoid mutant tau expression during the perinatal and early postnatal stages, thereby preventing possible developmental alterations unrelated to Alzheimer's disease.

Effect size of memory deficits in mice with adult-onset P301L tau expression.

Clinical experience has shown that examinees performing the Grooved Pegboard Test frequently have difficulty maintaining the manualized right-to-left placement direction with their left hand. To date, no empirical study has examined this phenomenon. The purpose of this study was to investigate whether left-hand peg placement direction (right-to-left vs. left-to-right) influences performance on this standardized test of fine motor speed and dexterity. The participants were 66 male and female student volunteers aged 18 to 58 years old. None of the participants had a history of neurologic disease/trauma or conditions that would affect motor functioning of the right and left upper extremities. Data were analyzed using a two-way mixed-design analysis of covariance. Results revealed a significant main effect for gender, F(1, 62) = 5.638, p = .021. Of primary interest was the main effect for placement direction, which was not significant, F(1, 62) = 0.108, p = .744. No significant interaction was observed, F(1, 62) = 0.002, p = .964.

Effect of Left-Hand Peg Placement Direction on the Grooved Pegboard Test.

Alzheimer's disease (AD) is the most common form of dementia in individuals over 65 years of age and is characterized by accumulation of beta-amyloid (Aβ) and tau. Both Aβ and tau alter synaptic plasticity, leading to synapse loss, neural network dysfunction, and eventually neuron loss. However, the exact mechanism by which these proteins cause neurodegeneration is still not clear. A growing body of evidence suggests perturbations in the glutamatergic tripartite synapse, comprised of a presynaptic terminal, a postsynaptic spine, and an astrocytic process, may underlie the pathogenic mechanisms of AD. Glutamate is the primary excitatory neurotransmitter in the brain and plays an important role in learning and memory, but alterations in glutamatergic signaling can lead to excitotoxicity. This review discusses the ways in which both beta-amyloid (Aβ) and tau act alone and in concert to perturb synaptic functioning of the tripartite synapse, including alterations in glutamate release, astrocytic uptake, and receptor signaling. Particular emphasis is given to the role of N-methyl-D-aspartate (NMDA) as a possible convergence point for Aβ and tau toxicity.

Article	Year
Correcting for gender on the Cognistat Judgment subtest. Applied neuropsychology. Adult\| PubMed ID: 23398001	2013
Effect size of memory deficits in mice with adult-onset P301L tau expression. Behavioural brain research\| PubMed ID: 25004446	2014
Effect of Left-Hand Peg Placement Direction on the Grooved Pegboard Test. Applied neuropsychology. Adult\| PubMed ID: 25584922	2015
The role of the tripartite glutamatergic synapse in the pathophysiology of Alzheimer's disease. Aging and disease\| PubMed ID: 25821641	2015

Daniel S. Weitzner

Biography

JoVE Journal Publications

Other Publications