Cheng Ke, Chen Chong, Deng Shilong, Xu Fei, Chen Xiangyu, Yang Jian, Wang Gang, Xie Peng
Chongqing Key Laboratory of Cerebrovascular Disease Research, Chongqing, 400016, China; Department of Neurology, Yongchuan Hospital of Chongqing Medical University, Chongqing, 400016, China.
NHC Key Laboratory of Diagnosis and Treatment on Brain Functional Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China; Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China.
J Affect Disord. 2025 Mar 15;373:186-195. doi: 10.1016/j.jad.2024.12.064. Epub 2024 Dec 23.
Major depressive disorder (MDD) is a destructive mental disease, yet the mechanism is still not clear. Carbonic anhydrase, an efficient catalyst for CO conversion to carbonate and protons, could affect many functions, such as memory formation recognition. Lately, we illustrated that carbonic anhydrase 1 (CAR1) knockout (CAR1) mice could lead to depressive-like behaviors, but the underlying molecular mechanism is unknown. Herein, we attempted to explore whether CAR1 knockout could result in transcriptional changes thus involve in depressive like behaviors. The present study revealed that compared with WT mice, the CAR1 Knockout (CAR1) mice led to depressive-like behavior. According to the microarray profiling, a couple of disturbed signaling pathways are found in CAR1 mice. Proteins like GluR1 and GABA Aα1 were validated compared to control groups by western blotting, while NMDAR 2A was increased in RNA level compared to the control group. More interestingly, the proteins might be related to the ERK signal pathway, MAPK, and RSK decreased in protein level compared to the control group. Moreover, this decline could be restored when CAR1 was overexpressed in the ventral hippocampus of CAR1 mice and depressive-like phenotypes were also rescued. Our dataset suggests that CAR1 might influence depressive-like behavior through the ERK signal pathway, which may provide novel insights and evidences to MDD study.
重度抑郁症（MDD）是一种具有破坏性的精神疾病，但其发病机制仍不清楚。碳酸酐酶是一种将CO转化为碳酸盐和质子的高效催化剂，它可以影响许多功能，如记忆形成识别。最近，我们发现碳酸酐酶1（CAR1）基因敲除（CAR1）小鼠会导致类似抑郁的行为，但其潜在的分子机制尚不清楚。在此，我们试图探讨CAR1基因敲除是否会导致转录变化，从而参与类似抑郁的行为。本研究表明，与野生型小鼠相比，CAR1基因敲除（CAR1）小鼠表现出类似抑郁的行为。根据微阵列分析，在CAR1小鼠中发现了一些受干扰的信号通路。通过蛋白质印迹法与对照组相比验证了GluR1和GABAAα1等蛋白质，而与对照组相比，NMDAR 2A的RNA水平升高。更有趣的是，与对照组相比，这些蛋白质可能与ERK信号通路、MAPK和RSK的蛋白质水平下降有关。此外，当在CAR1小鼠的腹侧海马体中过表达CAR1时，这种下降可以恢复，并且类似抑郁的表型也得到了挽救。我们的数据表明，CAR1可能通过ERK信号通路影响类似抑郁的行为，这可能为MDD研究提供新的见解和证据。
