Copper regulates rest-activity cycles through the locus coeruleus-norepineprhine system
| Autor: | Christopher J. Chang, Cheri M. Ackerman, Christine S. Liu, Bao Thai, Jefferson Y. Chan, Ehud Y. Isacoff, Adam Hoagland, Elizabeth C. Carroll, Tong Xiao, Shang Jia |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
ATP7A chemistry.chemical_element Article Arousal 03 medical and health sciences Norepinephrine Dopamine Biological neural network medicine Animals Molecular Biology Zebrafish biology Cell Biology medicine.disease biology.organism_classification Copper Cell biology 030104 developmental biology chemistry Locus coeruleus Locus Coeruleus Copper deficiency medicine.drug |
| Zdroj: | Nature chemical biology |
| ISSN: | 1552-4469 1552-4450 |
| Popis: | The unusually high demand for metals in the brain along with insufficient understanding of how their dysregulation contributes to neurological diseases motivates the study of how inorganic chemistry influences neural circuitry. We now report that the transition metal copper is essential for regulating rest–activity cycles and arousal. Copper imaging and gene expression analysis in zebrafish identifies the locus coeruleus-norepinephrine (LC-NE) system, a vertebrate-specific neuromodulatory circuit critical for regulating sleep, arousal, attention, memory and emotion, as a copper-enriched unit with high levels of copper transporters CTR1 and ATP7A and the copper enzyme dopamine beta-hydroxylase (DBH) that produces NE. Copper deficiency induced by genetic disruption of ATP7A, which loads copper into DBH, lowers NE levels and hinders LC function as manifested by disruption in rest–activity modulation. Moreover, LC dysfunction caused by copper deficiency from ATP7A disruption can be rescued by restoring synaptic levels of NE, establishing a molecular CTR1-ATP7A-DBH-NE axis for copper-dependent LC function. |
| Databáze: | OpenAIRE |
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