Effects of Calcium Mishandling in Astrocytic Mitochondria: The Unexplored Powerhouse
Abstract
Astrocytes are the most populous cell type in the central nervous system (CNS) and are vital in neuron development, regulating blood flow, and maintaining communication between neurons. Astrocytic control on the CNS is due in part to their complex morphology, consisting of a circular soma extending into primary branches that further divide into smaller branchlets and leaflets. The morphology of astrocytes allows calcium (Ca2+) to function as their main communicator, much like electrical signals in neurons. Increased Ca2+ in astrocytes causes gliotransmitter release, leading to regulation of synaptic transmission in neurons. The majority of Ca2+ signals in astrocytes originate in mitochondria, even within the nanometer sized branchlets and leaflets. Recent studies show Ca2+ mishandling in neuronal mitochondria leads to dysfunction and is associated with early neurodegeneration in Alzheimer’s and Parkinson’s disease. However, effects of Ca2+ mishandling in astrocytic mitochondria are less understood. Considering this, we will disrupt Ca2+ signaling specifically in astrocytic mitochondria using an adeno-associated virus (AAV) overexpressing neuronal Ca2+ sensor 1 (NCS1), a ubiquitous Ca2+ buffering protein. Under normal conditions, NCS1 functions in neurotransmitter release, cell growth and survival. However, NCS1 is upregulated in schizophrenia, bipolar disorder, and autism as well as Parkinson’s disease. In order to verify disruption of Ca2+ signaling via NCS1, our construct will first be assessed in the astrocytoma cell line, SMA-560. By assessing changes in morphology and respiration, as a result of Ca2+ mishandling, we hope to progress our understanding of the role this unexplored powerhouse plays in neurodegenerative diseases.
Subject
AstrocyteMitochondria
Calcium
NCS1
SMA-560
Neurodegenerative Disease
Morphology
Respiration
MitoGraph
Seahorse XFe96 Analyzer
Adeno-Associated Viral Vectors
Citation
Torres, Belen A; Huang Frazier, Megan (2021). Effects of Calcium Mishandling in Astrocytic Mitochondria: The Unexplored Powerhouse. Undergraduate Research Scholars Program. Available electronically from https : / /hdl .handle .net /1969 .1 /200659.