Exploring the role of SERCA2 in the mouse brain using novel transgenic and pharmacological mouse models.

Exploring the role of SERCA2 in the mouse brain using novel transgenic and pharmacological mouse models.

Presenter(s)

Hayden Ott

Comments

11:00-12:30, Kennedy Union 222

Description

Ca2+ homeostasis is critical for various neural processes such as neurotransmission and development. A key regulator of intracellular Ca2+-handling is the sarco-endoplasmic reticulum (SR/ER) Ca2+ ATPase (SERCA), which operates by sequestering cytosolic Ca2+ into the ER. Dysfunction of SERCA and Ca2+ homeostasis have been implicated in several debilitating neuropsychiatric conditions including schizophrenia, and attention-deficit hyperactivity disorder (ADHD). Our lab has recently reported that chronic pharmacological allosteric activation of SERCA via CDN1163, impact mouse behavior and the brain's neurochemistry in a sex-specific manner. Interestingly, we’ve additionally observed that phospholamban (PLN), a critical regulator of SERCA2 that has been well-studied with regard to its role in the heart, is also selectively expressed in the thalamic reticular nucleus (TRN) of the mouse brain. Using a novel transgenic mouse model, we have found that genetic ablation of PLN in this brain region induces an ADHD-like phenotype characterized by hyperactivity, impulsivity, and sleep-deficits. Currently, we are continuing to investigate the roles of the PLN and SERCA in the brain using genetic and pharmacological approaches in conjunction with neurochemical analyses, as well as behavioral and RNA/protein expression assessments. The results of these experiments have high potential to give us deep insights into the role of the PLN/SERCA2 pathway in the neurobiology of debilitating brain disorders.

Publication Date

4-23-2025

Project Designation

Graduate Research

Primary Advisor

Pothitos Pitychoutis

Primary Advisor's Department

Biology

Keywords

Stander Symposium, College of Arts and Sciences

Institutional Learning Goals

Scholarship; Critical Evaluation of Our Times

Exploring the role of SERCA2 in the mouse brain using novel transgenic and pharmacological mouse models.

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