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Dynamic Orexinergic Responses to Environmental Stressors in the Zebrafish Gut (2024)

Undergraduate: Yingning Sang


Faculty Advisor: Christina Graves
Department: Oral and Craniofacial Health Sciences


Objectives: The hypothalamic hypocretin (hcrt)/orexinergic system modulates sleep/wake cycles, arousal, and feeding. While orexinergic circuits have been well-described in the central nervous system, debate remains whether a bona fide circuit exists in the enteric nervous system. The primary objective of this study was to investigate the expression of hcrt and the hcrt receptor (hcrtr2) in the zebrafish gut using transcriptomic approaches; the secondary objective was to determine whether gut hcrt/hcrtr2 expression is modulated by chronic stress or feeding state._x000D_
Results: qPCR analysis revealed robust transcription of hcrt and hcrtr2 in the zebrafish gut, with significantly higher expression in the distal gut compared to the proximal gut. We also found that an overnight fast significantly increased expression of gut hcrt and hcrtr2 and that the distal gut is more responsive to the feeding state than proximal gut. Moreover, both brain and gut hcrt/hcrtr2 transcription was significantly impaired in fish exposed to chronic early life stress.    _x000D_
Conclusions: Our results describe for the first time the presence of an orexinergic system in the zebrafish gut, and that local expression is responsive to feeding state and is reduced following chronic stress.