Macroscopic imaging analysis of astrocytic Ca²⁺ activities in neurodegenerative disease model mouse

Abstract

Astrocyte is the predominant type of glial cell that attracts attention as a potential target of drug discovery and therapeutics for neurodegenerative diseases. Astrocytic Ca²⁺ signals are enhanced by neuronal hyperactivities and/or bioactive substances released from injured brain cells. Ca²⁺ signals can trigger Ca²⁺-dependent processes including various gene expressions and secretion of neuro-protective/toxic molecules in astrocytes. Thus, analysis of astrocytic Ca²⁺ signals may provide clues for the regulation of neurodegenerative diseases. Because it remains elusive how the pathological conditions affect astrocytic Ca²⁺ activities, we are trying to establish a new method to analyze astrocytic Ca²⁺ activities in neurodegenerative diseases. We applied a drug-induced or genetical neurodegenerative disease model to a transgenic mouse line that expresses a genetically encoded Ca²⁺ sensor, YC-Nano50, in astrocytes. We found disorder-related changes in astrocytic Ca²⁺ activities from macroscopic Ca²⁺ imaging analysis in the cortical surface of these mice. This method may clarify astrocytic Ca²⁺ activities in brain pathology and contribute to the development of therapeutic strategies for neurodegenerative diseases.