Mitochondrial dysfunction contributes to neurodegenerative diseases and developmental disorders such as Fragile X syndrome (FXS). The cross-talk between mitochondria and extracellular vesicles (EVs) suggests that EVs may transfer mitochondrial components as intermediators for intracellular communication under physiological and pathological conditions. In the present study, the ability of EVs to transfer mitochondrial components and their role in mitochondrial dysfunction in astrocytes were examined in the brains of Fmr1 knockout (KO) mice, a model of FXS. The amounts of mitochondrial transcription factor NRF-1, ATP synthases ATP5A and ATPB, and the mitochondrial membrane protein VDAC1 in EVs were reduced in cerebral cortex samples and astrocytes from Fmr1 KO mice. These reductions correspond to decreased mitochondrial biogenesis and transcriptional activities in Fmr1 KO brain, along with decreased mitochondrial membrane potential (MMP) with abnormal localization of vimentin intermediate filament (VIF) in Fmr1 KO astrocytes. Our results suggest that mitochondrial dysfunction in astrocytes is associated with the pathogenesis of FXS and can be monitored by depletion of components in EVs. These findings may improve the ability to diagnose developmental diseases associated with mitochondrial dysfunction, such as FXS and autism spectrum disorders (ASD).

Neuroscience research has become a national priority for the Korean government. Korean scholars have dedicated interest in the societal ramifications of neurotechnologies; neuroethics is an integral component of the Korea Brain Initiative and to the formation of its growing neuroscience community.

Tae-Woo Kang, Tai-Won Oh and Sung-Jin Jeong. Exp Neurobiol 2023;32:1-7. https://doi.org/10.5607/en22037

The extracellular matrix (ECM) components present within all tissues and organs help to maintain the cytoskeletal architecture and tissue morphology. Although the ECM plays a role in cellular events and signaling pathways, it has not been well studied due its insolubility and complexity. Brain tissue has a higher cell density and weaker mechanical strength than other tissues in the body. When removing cells using a general decellularization method to produce scaffolds and obtain ECM proteins, various problems must be considered because tissues are easily damaged. To retain the brain shape and ECM components, we performed decellularization in combination with polymerization. We immersed mouse brains in oil for polymerization and decellularization via O-CASPER (Oil-based Clinically and Experimentally Applicable Acellular Tissue Scaffold Production for Tissue Engineering and Regenerative Medicine) and then isolated ECM components using sequential matrisome preparation reagents (SMPRs), namely, RIPA, PNGase F, and concanavalin A. Adult mouse brains were preserved with our decellularization method. Western blot and LC-MS/MS analyses revealed that ECM components, including collagen and laminin, were isolated efficiently from decellularized mouse brains using SMPRs. Our method will be useful to obtain matrisomal data and perform functional studies using adult mouse brains and other tissues.

The ADGRG1 gene encodes GPR56, an adhesion G-protein-coupled receptor essential for neuronal migration during cortical development. GPR56 interacts with extracellular matrix components such as collagen III, integrin α3β1, and tetraspanins CD81/CD9. While prior studies demonstrated cortical dysplasia in collagen III single knockout and GPR56/Itga3 double knockout mice, the role of CD81 in brain development remains unclear. This study investigates the functional interaction between CD81 and GPR56 in the embryonic brain. We found CD81 highly expressed in apical and basal regions and the meninges of the developing neocortex. CD81 was detected with GPR56 in neurons and astrocytes and expressed in collagen III⁺ meningeal fibroblasts (MFs) and CD34⁺ endothelial cells. CD81 directly interacted with GPR56 in neurons and with collagen III in MFs. In neurons, CD81 was required for collagen III-induced activation of the GPR56-RhoA signaling pathway. In MFs, CD81 depletion reduced vimentin and collagen III levels, indicating impaired meningeal integrity. Notably, Gpr56/Cd81 double knockout mice exhibited severe frontal brain malformations, including neuronal over-migration and cortical dyslamination. These findings show a cooperative role of CD81 with GPR56 and collagen III in both neural and meningeal compartments, contributing to proper cortical formation during embryonic development.