Hippocampus carbonic anhydrase 1 via ERK pathway may be involved in depressive like behaviors.

Abstract

Major depressive disorder (MDD) is a destructive mental disease, yet the mechanism is still not clear. Carbonic anhydrase, an efficient catalyst for COconversion 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 CAR1mice. 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 CAR1mice 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.