PUBLICATION
Panx1a modulates metabolic stress signaling and synaptic composition in the developing zebrafish brain
- Authors
- Zoidl, G.S.O., Safarian, N., Zoidl, C., Connor, S., Zoidl, G.R.
- ID
- ZDB-PUB-251112-4
- Date
- 2025
- Source
- Cell and tissue research 402: 217-242 (Journal)
- Registered Authors
- Safarian, Nickie, Zoidl, Christiane, Zoidl, Georg
- Keywords
- ATP signaling, Metabolic stress, Panx1a, Synaptic plasticity, Zebrafish
- MeSH Terms
-
- Animals
- Brain*/embryology
- Brain*/growth & development
- Brain*/metabolism
- Connexins*/metabolism
- Oxidative Stress
- Signal Transduction*
- Stress, Physiological*
- Synapses*/metabolism
- Zebrafish*/embryology
- Zebrafish*/metabolism
- Zebrafish Proteins*/genetics
- Zebrafish Proteins*/metabolism
- PubMed
- 41217516 Full text @ Cell Tissue Res.
Citation
Zoidl, G.S.O., Safarian, N., Zoidl, C., Connor, S., Zoidl, G.R. (2025) Panx1a modulates metabolic stress signaling and synaptic composition in the developing zebrafish brain. Cell and tissue research. 402:217-242.
Abstract
Pannexin 1a (Panx1a), a neuronal ATP-release channel, is increasingly recognized for its role in neurodevelopment, yet its contribution to synaptic homeostasis under metabolic stress remains poorly defined. We demonstrate that Panx1a coordinates synaptic and metabolic processes supporting neural circuit stability in the developing zebrafish brain. Using a genetic Panx1a knockout model and pharmacological induction of oxidative stress via MPTP, we reveal that Panx1a loss exacerbates metabolic alterations, reduces extracellular ATP availability, and triggers transcriptional activation of AMPK-mTORC1 signaling, autophagy, and apoptosis. These molecular changes coincide with impaired synaptic gene expression and increased neuronal cell death, particularly in the tectum and pallium. Electrophysiological recordings further show that Panx1a may function as a regulator for preserving local field potential coherence and phase-amplitude coupling, with knockout larvae displaying aberrant oscillatory activity and reduced network adaptability. Our findings identify Panx1a as a regulator of the metabolic-synaptic interface during a vulnerable developmental window and suggest that its ablation could contribute to pathophysiological mechanisms underlying neurodevelopmental disorders.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping