Astrocyte-Targeted Biomarkers for Calcitonin Gene-Related Peptide-Related Neurovascular Disorders: Insights from...

Advancing our understanding of astrocyte-mediated neurochemical communication and the role that calcium plays in astrocyte function may ultimately enable the development of strategies for diagnosing, treating, and preventing conditions that involve astrocyte dysfunction, including calcitonin gene-related peptide (CGRP)-based neurovascular disorders. We investigated the utility of intracellular calcium concentration and metabolic changes as potential indicators of astrocyte dysfunction. We used CGRP to induce cellular dysfunction in CTX-TNA2 astrocytes and examined the relationship between astrocyte dysfunction and intracellular calcium levels using inductively coupled plasma-optical emission spectrometry. In addition, we compared the metabolic and neurochemical profiles of untreated (control) astrocytes with those of CGRP- and CaCl₂-treated astrocytes. Higher intracellular calcium concentrations were observed in the CGRP-treated astrocytes. Glucose metabolites exhibited chemical shifts in the control and CaCl₂-treated astrocytes but were less evident in CGRP-treated astrocytes, suggesting potential alterations in glucose metabolism. The CGRP-treated astrocytes also had significantly lower levels of creatine (Cr), the glutamate-glutamine complex (Glx), and myo-inositol than the control astrocytes. The Cr and myo-inositol levels were significantly higher in the CaCl₂-treated astrocytes than in the control astrocytes. Our findings suggest that monitoring the intracellular calcium concentration and metabolic profile can be a valuable approach for detecting early astrocyte dysfunction. The metabolic and neurochemical changes induced by CGRP highlight the potential of astrocyte-targeted strategies for mitigating CGRP-related neurovascular disorders.