Abstract Title

The effects of blocking amylin receptors on oxidative stress and neuroinflammation in APP/PS1 mice.

Abstract

Oxidative stress and neuroinflammation are key pathologies in neurodegenerative diseases, such as Alzheimer’s Disease (AD). Amylin is a peptide hormone that has been previously shown in our lab to have therapeutic effects in patients with AD, specifically, reducing said pathologies. Pramlintide (PRAM) is the mouse analog of amylin that is non aggregating and is being used in this experiment. The mechanism of action of PRAM is unclear and is being investigated in this study. Our main question is whether the therapeutic effects of PRAM are a result of the regulation of PRAM centrally through its receptor in the brain, or if these benefits are due to increases in overall metabolic function, and these will be tested on APP/PS1 mice, a mouse model of AD. This was investigated by administering chronic PRAM peripherally, with and without the amylin receptor antagonist (AC187) via ICV. Brain tissue was collected from these mice and immunohistochemistry was carried out for different oxidative stress and inflammation markers present across treatment groups. Preliminary results show a decrease in oxidative stress and inflammation markers mainly when PRAM is administered without the inhibitor. Together this suggests that amylin’s therapeutic effects are dependent on the amylin receptor, and in turn, shows a central role of amylin’s normal functionality.

Modified Abstract

Oxidative stress and neuroinflammation are key pathologies Alzheimer’s Disease (AD). Amylin is a peptide hormone that has therapeutic effects in AD patients, specifically, reducing said pathologies. Pramlintide (PRAM), the mouse analog of amylin has an unclear mechanism of action and is the target of our investigation. Whether the therapeutic effects of PRAM are a result of the regulation of PRAM centrally, or if these benefits are due to increases in overall metabolic function will be tested on APP/PS1 mice. IHC preliminary results show a decrease in oxidative stress and inflammation markers mainly when PRAM is administered without the inhibitor. Together this suggests that amylin’s therapeutic effects are dependent on the amylin receptor, therefore, showing a central role of amylin’s normal functionality.

Research Category

Biomedical Sciences

Primary Author's Major

Biology

Mentor #1 Information

Sabina Bhatta

Mentor #2 Information

Rachel Corrigan

Mentor #3 Information

John Grizzanti

Mentor #4 Information

Dr. Gemma Casadesus-Smith

Presentation Format

Poster

Start Date

5-4-2018 1:00 PM

Research Area

Biology | Life Sciences

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Apr 5th, 1:00 PM

The effects of blocking amylin receptors on oxidative stress and neuroinflammation in APP/PS1 mice.

Oxidative stress and neuroinflammation are key pathologies in neurodegenerative diseases, such as Alzheimer’s Disease (AD). Amylin is a peptide hormone that has been previously shown in our lab to have therapeutic effects in patients with AD, specifically, reducing said pathologies. Pramlintide (PRAM) is the mouse analog of amylin that is non aggregating and is being used in this experiment. The mechanism of action of PRAM is unclear and is being investigated in this study. Our main question is whether the therapeutic effects of PRAM are a result of the regulation of PRAM centrally through its receptor in the brain, or if these benefits are due to increases in overall metabolic function, and these will be tested on APP/PS1 mice, a mouse model of AD. This was investigated by administering chronic PRAM peripherally, with and without the amylin receptor antagonist (AC187) via ICV. Brain tissue was collected from these mice and immunohistochemistry was carried out for different oxidative stress and inflammation markers present across treatment groups. Preliminary results show a decrease in oxidative stress and inflammation markers mainly when PRAM is administered without the inhibitor. Together this suggests that amylin’s therapeutic effects are dependent on the amylin receptor, and in turn, shows a central role of amylin’s normal functionality.