Advances in cell-based therapies targeting inhibitory neurons for schizophrenia: a novel strategy to address negative symptoms and cognitive deficits
10.3760/cma.j.cn113661-20250407-00165
- VernacularTitle:基于抑制性神经元的精神分裂症细胞治疗研究进展：突破阴性症状与认知缺陷的新策略
- Author:
Chuqing ZHOU
1
;
Jun ZHAO
1
;
Youhui JIANG
1
;
Xinyi REN
1
;
Tao LI
1
;
Peiyan NI
1
Author Information
1. 杭州第七人民医院 浙江大学医学院附属精神卫生中心，杭州 310013
- Publication Type:Journal Article
- Keywords:
Schizophrenia;
Negative symptoms;
Cognitive deficits;
Inhibitory GABAergic interneurons;
Induced pluripotent stem cells;
Cell therapy
- From:
Chinese Journal of Psychiatry
2025;58(11):862-869
- CountryChina
- Language:Chinese
-
Abstract:
Schizophrenia is a chronic, severe, and highly heterogeneous psychiatric disorder. Current antipsychotic medications show limited effectiveness in treating negative symptoms and cognitive deficits. Accumulating evidence suggests that dysfunction of inhibitory γ-aminobutyric acid (GABA) neurons, leading to inhibitory circuit dysregulation, plays a pivotal role in the pathophysiology of the disorder. Recent advances in induced pluripotent stem cells (iPSCs) and brain organoid technologies have provided more accurate human-based models of schizophrenia, offering new avenues to investigate the complex neurodevelopmental mechanism of schizophrenia and to explore cell replacement therapies. Preclinical studies have demonstrated that transplantation of specific types of GABAergic interneuron precursors into the brain can selectively improve negative symptoms and cognitive deficits in animal models, highlighting considerable translational potential. However, the transition from bench to bedside still faces multiple technical and ethical challenges, enhancing cell differentiation efficiency, ensuring long-term safety of transplanted cells, achieving precise control and functional integration of neuronal subtypes, understanding circuit-specific contributions to different symptom domains, and establishing rigorous ethical and regulatory frameworks. In summary, inhibitory GABAergic interneuron-based cell therapy provides a novel theoretical and perspective foundation for improving negative and cognitive symptoms of schizophrenia. Despite significant challenges ahead, its prospects remain highly promising.
