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<p>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.</p>

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Panx1a modulates metabolic stress signaling and synaptic composition in the developing zebrafish brain

  • 期刊论文

  • 发表日期：

    2025年11月11日

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  • Georg S. O. Zoidl,
  • Nickie Safarian,
  • Christiane Zoidl,
  • Steven Connor,
  • Georg R. Zoidl

摘要

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.