Acta Neuropathologica Communications (Apr 2023)

Upregulation of carbonic anhydrase 1 beneficial for depressive disorder

  • Ke Cheng,
  • Yue Wang,
  • Yong He,
  • Yu Tian,
  • Junjie Li,
  • Chong Chen,
  • Xingzhe Xu,
  • Zhonghao Wu,
  • Heming Yu,
  • Xiangyu Chen,
  • Yili Wu,
  • Weihong Song,
  • Zhifang Dong,
  • Huatai Xu,
  • Peng Xie

DOI
https://doi.org/10.1186/s40478-023-01545-6
Journal volume & issue
Vol. 11, no. 1
pp. 1 – 14

Abstract

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Abstract Carbonic Anhydrase 1 (CAR1) is a zinc-metalloenzyme that catalyzes the hydration of carbon dioxide, and the alteration of CAR1 has been implicated in neuropsychiatric disorders. However, the mechanism underlying the role of CAR1 in major depressive disorder (MDD) remains largely unknown. In this study, we report the decreased level of CAR1 in MDD patients and depression-like model rodents. We found that CAR1 is expressed in hippocampal astrocytes and CAR1 regulates extracellular bicarbonate concentration and pH value in the partial hilus. Ablation of the CAR1 gene increased the activity of granule cells via decreasing their miniature inhibitory postsynaptic currents (mIPSC), and caused depression-like behaviors in CAR1-knockout mice. Astrocytic CAR1 expression rescued the deficits in mIPSCs of granule cells and reduced depression-like behaviors in CAR1 deficient mice. Furthermore, pharmacological activation of CAR1 and overexpression of CAR1 in the ventral hippocampus of mice improved depressive behaviors. These findings uncover a critical role of CAR1 in the MDD pathogenesis and its therapeutic potential.

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