Calcium and activity-dependent signaling in the developing cerebral cortex

Abstract

Calcium influx can be stimulated by various intra- and extracellular signals to set coordinated gene expression programs into motion. As such, the precise regulation of intracellular calcium represents a nexus between environmental cues and intrinsic genetic programs. Mounting genetic evidence points to a role for the deregulation of intracellular calcium signaling in neuropsychiatric disorders of developmental origin. These findings have prompted renewed enthusiasm for understanding the roles of calcium during normal and dysfunctional prenatal development. In this Review, we describe the fundamental mechanisms through which calcium is spatiotemporally regulated and directs early neurodevelopmental events. We also discuss unanswered questions about intracellular calcium regulation during the emergence of neurodevelopmental disease, and provide evidence that disruption of cell-specific calcium homeostasis and/or redeployment of developmental calcium signaling mechanisms may contribute to adult neurological disorders. We propose that understanding the normal developmental events that build the nervous system will rely on gaining insights into cell type-specific calcium signaling mechanisms. Such an understanding will enable therapeutic strategies targeting calcium-dependent mechanisms to mitigate disease.

Homo sapiens—A Species Not Designed for Space Flight: Health Risks in Low Earth Orbit and Beyond, Including Potential Risks When Traveling beyond the Geomagnetic Field of Earth

“…As calcium is well known to be an important regulator of many enzyme systems and biochemical pathways, the blood levels are tightly regulated and much of the liberated calcium is likely removed from the body by the kidneys and then ends up in the urine. Calcium signaling is important in the heart and vascular systems [ 19 , 20 , 21 , 22 ], in the brain [ 23 , 24 , 25 ], and in other tissues [ 26 , 27 ]. Some individuals who are at risk for kidney stones or gout could suffer from the consequences of high levels of calcium, and some biological systems may also be affected if the removal is not sufficient once the increases in calcium liberation become chronic and a secondary disease risk develops that was not evident on Earth.…”

EP1 receptor: Devil in emperors coat

“…22 Calcium (Ca 2+ ) is an important secondary messenger molecule and regulates the activity of many signaling molecules and proteins. 23,24 The concentration of Ca 2+ ions significantly increases in AD and plays an important role in the pathology of this disease. 25 It has also been found that an increased Ca2+ level is involved in the hyperphosphorylation of tau in AD.…”

Distinct calcium sources regulate temporal profiles of NMDAR and mGluR-mediated protein synthesis

“…Although calcium release from the Endoplasmic Reticulum (ER) and store-operated calcium entry (SOCE) are common mechanisms in all cell types, neurons have additional contributions through Voltage-Gated Calcium Channels (VGCCs) and calcium-permeable ionotropic glutamate receptors such as NMDA receptors (NMDARs). Thus, in neurons, NMDARs, VGCCs, SOCE, and ER-mediated calcium release are the major routes contributing to local and global calcium elevations and activation of intracellular signaling pathways ( 2 , 3 , 4 , 5 ). Many processes in neurons, such as gene expression, transcription, and alternative splicing, are shown to be regulated in a calcium-dependent and calcium channel–specific manner ( 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 ).…”