Insights into the role of intracellular calcium signaling in the neurobiology of neurodevelopmental disorders
Benjamin Klocke, Kylie Krone, Jason Tornes, Carter Moore, Hayden Ott, Pothitos M. Pitychoutis
Abstract
Calcium (Ca 2+ ) comprises a critical ionic second messenger in the central nervous system that is under the control of a wide array of regulatory mechanisms, including organellar Ca 2+ stores, membrane channels and pumps, and intracellular Ca 2+ -binding proteins. Not surprisingly, disturbances in Ca 2+ homeostasis have been linked to neurodegenerative disorders, such as Alzheimer’s and Parkinson’s diseases. However, aberrations in Ca 2+ homeostasis have also been implicated in neuropsychiatric disorders with a strong neurodevelopmental component including autism spectrum disorder (ASD) attention-deficit hyperactivity disorder (ADHD) and schizophrenia (SCZ). While plasma membrane Ca 2+ channels and synaptic Ca 2+ -binding proteins have been extensively studied, increasing evidence suggests a prominent role for intracellular Ca 2+ stores, such as the endoplasmic reticulum (ER), in aberrant neurodevelopment. In the context of the current mini-review, we discuss recent findings implicating critical intracellular Ca 2+ -handling regulators such as the sarco-ER Ca 2+ ATPase 2 (SERCA2), ryanodine receptors (RyRs), inositol triphosphate receptors (IP 3 Rs), and parvalbumin (PVALB), in the emergence of ASD, SCZ, and ADHD.