Dopamine Triggers CTCF-Dependent Morphological and Genomic Remodeling of Astrocytes

• DOI: 10.1523/jneurosci.3349-17.2018
• Publication Date: 2018-04-30T15:35:42Z
• Authors: Ashley Galloway; Adewale Adeluyi; Bernadette O'Donovan; Miranda L. Fisher; Chintada Nageswar...; Peyton Critchfield; Mathew Sajish; Jill R. Turner; Pavel I. Ortinski
• Keywords: CTCF

Dopamine is critical for processing of reward and etiology drug addiction. Astrocytes throughout the brain express dopamine receptors, but consequences astrocytic receptor signaling are not well established. We found that extracellular triggered rapid concentration-dependent stellation processes was a result oxidation instead relied on both cAMP-dependent cAMP-independent signaling. This accompanied by reduced duration increased frequency Ca 2+ transients, little effect voltage-gated potassium channel currents. To isolate possible mechanisms underlying these structural functional changes, we used whole-genome RNA sequencing prominent dopamine-induced enrichment genes containing CCCTC-binding factor (CTCF) motif, suggesting involvement chromatin restructuring in nucleus. CTCF binding to promoter sites bidirectionally regulates gene transcription depends activation poly-ADP-ribose polymerase 1 (PARP1). Accordingly, antagonism PARP1 occluded whereas agonist facilitated changes its own. These results indicate astrocyte response elevated involves PARP1-mediated genomic concerted expression networks. Our findings propose epigenetic regulation landscape as dopamine. SIGNIFICANCE STATEMENT Although widely recognized role modulating neuronal responses healthy disease states, known about effects at non-neuronal cells brain. address this gap, performed astrocytes exposed combined it with evaluation morphology function. demonstrate temporally dynamic pattern plasticity triggers pronounced further show sensitive DNA-binding protein CTCF. broad specifically relies CTCF-dependent