Project Title

The Effects of a Novel Anti-inflammatory on Behavioral Tests of Cognition and Anxiety in a Mouse Model of Alzheimer’s Disease

Authors' Affiliations

Hannah Rauhuff, Drew Gill, Heath Shelton, Cody Kerns, and Russell Brown, Department of Biomedical Sciences, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, TN. Prasad Gabbita, P2D Bioscience, Inc., Cincinnati, OH.

Location

Ballroom

Start Date

4-12-2019 9:00 AM

End Date

4-12-2019 2:30 PM

Poster Number

28

Faculty Sponsor’s Department

Biomedical Sciences

Name of Project's Faculty Sponsor

Dr. Russell Brown

Type

Poster: Competitive

Classification of First Author

Undergraduate Student

Project's Category

Neuroscience, Alzheimers Disease

Abstract Text

Alzheimer’s disease (AD) is a progressive neurodegenerative disease that results in severe cognitive impairment and eventually is fatal. In addition to memory loss, AD patients also present with psychosis and emotional psychological symptoms. Neuropathologically, the disease is characterized by aggregation of amyloid-beta protein that accumulates into plaques and hyperphosporylation of tau protein which results in neurofibrillary tangles. Further, neuropathology in AD results in broad neuroinflammation. In recent years, there has been a research focus on novel treatments for AD because current medications have not been particularly effective and have significant side effects. In the current study, we analyzed whether PD340, a novel anti-inflammatory which inhibits the pro-inflammatory cytokine tumor necrosis factor-alpha (TNFα) would be effective to alleviate behavioral impairments in the 3xTg mouse model of AD. The 3xTg model is unique in comparison to previous rodent models of AD because it express three dementia-related transgenes and demonstrates a clear age-dependent onset of AD pathology. Mice were bred in our animal colony. Beginning at four months of age, a specialized diet was presented to the animals that contained 0, 3, 10, or 25 mg/kg of PD340. At approximately 6 months of age, which is before any neuropathology presents in this model, animals were behaviorally tested on three different tasks: The Barnes maze, which is a test of spatial memory; Prepulse inhibition (PPI), which is a measure of sensorimotor gating and is related to psychosis and cognition; and the elevated T-maze, which is a test of anxiety. Both males and females were tested. Results from Barnes maze testing revealed that females, but not males, administered 25 mg/kg of PD340 demonstrated a significant improvement in spatial bias towards the goal during acquisition. Regarding PPI, there were no sex differences, but groups receiving the 3 or 25 mg/kg dose of PD340 demonstrated significantly improved performance over animals administered the 0 mg/kg dose of PD340 dependent upon the auditory decibel level of the stimulus presented. On the elevated T-maze, there were no significant group differences, demonstrating anxiety is not present at 6 months of age in this model. Behavioral tests will also be performed at 12 and 15 months of age in these animals. However, at 6 months of age, it appears that PD340 is effective in alleviating behavioral deficits related to cognitive impairment in a mouse model of AD. Future work will analyze neuropathology in the hippocampus and prefrontal cortex, two brain areas that degenerate in AD and are important in cognitive function.

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Apr 12th, 9:00 AM Apr 12th, 2:30 PM

The Effects of a Novel Anti-inflammatory on Behavioral Tests of Cognition and Anxiety in a Mouse Model of Alzheimer’s Disease

Ballroom

Alzheimer’s disease (AD) is a progressive neurodegenerative disease that results in severe cognitive impairment and eventually is fatal. In addition to memory loss, AD patients also present with psychosis and emotional psychological symptoms. Neuropathologically, the disease is characterized by aggregation of amyloid-beta protein that accumulates into plaques and hyperphosporylation of tau protein which results in neurofibrillary tangles. Further, neuropathology in AD results in broad neuroinflammation. In recent years, there has been a research focus on novel treatments for AD because current medications have not been particularly effective and have significant side effects. In the current study, we analyzed whether PD340, a novel anti-inflammatory which inhibits the pro-inflammatory cytokine tumor necrosis factor-alpha (TNFα) would be effective to alleviate behavioral impairments in the 3xTg mouse model of AD. The 3xTg model is unique in comparison to previous rodent models of AD because it express three dementia-related transgenes and demonstrates a clear age-dependent onset of AD pathology. Mice were bred in our animal colony. Beginning at four months of age, a specialized diet was presented to the animals that contained 0, 3, 10, or 25 mg/kg of PD340. At approximately 6 months of age, which is before any neuropathology presents in this model, animals were behaviorally tested on three different tasks: The Barnes maze, which is a test of spatial memory; Prepulse inhibition (PPI), which is a measure of sensorimotor gating and is related to psychosis and cognition; and the elevated T-maze, which is a test of anxiety. Both males and females were tested. Results from Barnes maze testing revealed that females, but not males, administered 25 mg/kg of PD340 demonstrated a significant improvement in spatial bias towards the goal during acquisition. Regarding PPI, there were no sex differences, but groups receiving the 3 or 25 mg/kg dose of PD340 demonstrated significantly improved performance over animals administered the 0 mg/kg dose of PD340 dependent upon the auditory decibel level of the stimulus presented. On the elevated T-maze, there were no significant group differences, demonstrating anxiety is not present at 6 months of age in this model. Behavioral tests will also be performed at 12 and 15 months of age in these animals. However, at 6 months of age, it appears that PD340 is effective in alleviating behavioral deficits related to cognitive impairment in a mouse model of AD. Future work will analyze neuropathology in the hippocampus and prefrontal cortex, two brain areas that degenerate in AD and are important in cognitive function.