Parvalbumin Interneuron Activation-Dependent Adult Hippocampal Neurogenesis Is Required for Treadmill Running to Reverse Schizophrenia-Like Phenotypes

Yandong Yi; Yuanlong Song; Yisheng Lu

doi:10.3389/fcell.2020.00024

Parvalbumin Interneuron Activation-Dependent Adult Hippocampal Neurogenesis Is Required for Treadmill Running to Reverse Schizophrenia-Like Phenotypes

Front Cell Dev Biol. 2020 Feb 4:8:24. doi: 10.3389/fcell.2020.00024. eCollection 2020.

Authors

Yandong Yi^{1

2}, Yuanlong Song^{1

3}, Yisheng Lu^{1

3}

Affiliations

¹ Department of Physiology, School of Basic Medicine, Huazhong University of Science and Technology, Wuhan, China.
² Department of Pharmacy, Wuhan No. 1 Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
³ Institute of Brain Research, Collaborative Innovation Center for Brain Science, Huazhong University of Science and Technology, Wuhan, China.

Abstract

Physical exercise can alleviate some of the schizophrenia symptoms in patients, the mechanisms, however, are still unclear. To investigate whether the GABAergic interneuron involved in the therapeutic effect of treadmill running on schizophrenia, the parvalbumin (PV)-positive GABAergic interneurons in the dentate gyrus (DG) was specifically activated or abolished and the effects were evaluated. In the MK801-induced schizophrenia-like animal model, we found:(1) Treadmill running rescued the schizophrenia-related behavioral phenotypes, promoted the adult hippocampal neurogenesis, and increased the dendrite number and complexity of newborn neurons. (2) Treadmill running increased the number of PV-positive interneurons in the DG; genetic ablation of these interneurons reduced adult neurogenesis and abolished the effect of treadmill running on the schizophrenia-related behaviors. Consistently, chemogenetic activation of these interneurons improved neurogenesis and alleviated the schizophrenia-related behaviors. These results suggest a pivotal role of PV-positive interneuron-mediated adult neurogenesis in exercise. (3) However, schizophrenia-related behavioral phenotypes and adult neurogenesis in the DG could still be reversed by exercise after specifically knocking out the schizophrenia-related gene ErbB4 in PV interneurons, as a means to reduce their GABA release. These results suggest that activation of PV interneurons in the DG is sufficient for treadmill running to reverse schizophrenia-like phenotypes.

Keywords: ErbB4; adult neurogenesis; hippocampus; parvalbumin; schizophrenia; treadmill running.