Effects of Chronic Pharmacological SERCA Activation on Amino Acid Neurochemistry and Dendritic Spine Density in the Mouse Brain

Date of Award

8-1-2024

Degree Name

M.S. in Biology

Department

Department of Biology

Advisor/Chair

Pothitos Pitychoutis

Abstract

Intracellular Calcium (Ca2+) signaling plays a crucial role in a multitude of critical neuronal processes that range from cell development and long-term potentiation, to neurotransmission and programed cell death. One key regulator of intracellular Ca2+ handling is the Sarco/Endoplasmic Reticulum (ER) Ca2+ ATPase (SERCA) pump. SERCA is responsible for sequestering cytosolic Ca2+ into the ER, a major site for Ca2+ storage. Due to its importance in maintaining Ca2+ homeostasis, it comes as no surprise that dysfunction of SERCA has been shown to be involved in various neuropsychiatric diseases, such as Parkinson’s Disease (PD), Alzheimer’s Disease (AD), and Schizophrenia. Consequently, drugs that affect the function of SERCA are of high interest for future therapeutic treatments, but the role that SERCA plays in the brain and behavior is not well understood. In the context of the current thesis, we assessed the effects of chronic pharmacological SERCA activation using the drug CDN1163 on amino acidergic neurochemical responses and dendritic spine density in brain regions implicated in cognitive processes in mice of both sexes. Taken together, the findings of the current study provide initial insights into the role that SERCA activation may play the regulation of amino acidergic neurotransmission and synaptic plasticity, and provides the necessary premise needed to allow for more refined and targeted neurobiological assessments to understand the role of SERCA activation in the brain and behavior.

Keywords

SERCA; CDN1163; Alzheimer's Disease; Parkinson's Disease; Neuroscience; Neurochemistry; Dendritic Spine Density

Rights Statement

Copyright © 2024, author.

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