PGAM5 knockout causes depressive-like behaviors in mice via ATP deficiency in the prefrontal cortex.

INTRODUCTION: Major depressive disorder (MDD) affects about 17% population in the world. Although abnormal energy metabolism plays an important role in the pathophysiology of MDD, however, how deficiency of adenosine triphosphate (ATP) products affects emotional circuit and what regulates ATP synthesis are still need to be elaborated. AIMS: Our study aimed to investigate how deficiency of PGAM5-mediated depressive behavior. RESULTS: We firstly discovered that PGAM5 knockout (PGAM5-/- ) mice generated depressive-like behaviors. The phenotype was reinforced by the observation that chronic unexpected mild stress (CUMS)-induced depressive mice exhibited lowered expression of PGAM5 in prefrontal cortex (PFC), hippocampus (HIP), and striatum. Next, we found, with the using of functional magnetic resonance imaging (fMRI), that the functional connectivity between PFC reward system and the PFC volume were reduced in PGAM5-/- mice. PGAM5 ablation resulted in the loss of dendritic spines and lowered density of PSD95 in PFC, but not in HIP. Finally, we found that PGAM5 ablation led to lowered ATP concentration in PFC, but not in HIP. Coimmunoprecipitation study showed that PGAM5 directly interacted with the ATP F1 F0 synthase without influencing the interaction between ATP F1 F0 synthase and Bcl-xl. We then conducted ATP administration to PGAM5-/- mice and found that ATP could rescue the behavioral and neuronal phenotypes of PGAM5-/- mice. CONCLUSIONS: Our findings provide convincing evidence that PGAM5 ablation generates depressive-like behaviors via restricting neuronal ATP production so as to impair the number of neuronal spines in PFC.

Deciphering the neural mechanisms of miR-134 in major depressive disorder with population-based and person-specific imaging transcriptomic techniques.

MiR-134 has emerged as a potential molecular biomarker for the detection and management of major depressive disorder (MDD). Nevertheless, the specific effects of miR-134 as a regulatory element on brain function and its implications for the clinical presentation of MDD are not yet fully understood. In order to investigate the potential neural mechanisms that contribute to the relationship between miR-134 and MDD, we employed a parallel two-stage cross-scale multi-omics approach. This involved utilizing the anterior cingulate cortex (ACC) functional connectivity as a means to connect microscopic molecular structures with macroscopic brain function in two separate cohorts: the MDD-I dataset (56 MDD patients and 51 healthy controls) and the MDD-II dataset (57 MDD patients and 52 healthy controls). We found a stable ACC functional dysconnectivity pattern of MDD and established the hierarchical cross-scale association from molecular organizations of miR-134 target genes to macroscopic brain functional dysconnectivity and associated behavior, as revealed by population-based analysis. Additionally, our person-specific imaging transcriptomic study revealed that individual exosomal miR-134 expression levels impact on individual clinical symptoms of MDD by modulating ACC-related functional dysconnectivity. Together, our findings provide compelling evidence of the correlation between miR-134 and depression across multi scales within the gene-brain-behavior context.

Advances in the role of exosomal non-coding RNA in the development, diagnosis, and treatment of gastric cancer (Review).

Exosomes are small vesicles secreted by a variety of cells that contain vrious biological macromolecules, including RNA, non-coding RNA and protein. An increasing number of studies have demonstrated that exosomes and particularly the non-coding RNAs they contain, serve important roles in many cellular processes, including the transmission of information. It is well established that the occurrence and development of gastric cancer, one of the four most common malignant tumors worldwide, involves the transmission of information. Based on the urgent need for the elucidation of the mechanism involved in this process, as well as advances in the diagnosis and treatment of gastric cancer, numerous reports have assessed the association between non-coding RNAs in exosomes and gastric cancer. The purpose of the present review was to summarize recent evidence on certain non-coding RNAs associated with the development, diagnosis and treatment of gastric cancer.