Transmembrane protein 108 (Tmem108) is a risk gene of psychiatric diseases including schizophrenia, bipolar disorder and major depression disorder. However, the pathophysiological mechanisms of Tmem108 are largely unknown. Here we investigated the pathophysiological function of Tmem108 in the hippocampal dentate gyrus by using Tmem108 mutant mice. Tmem108 highly expressed in the dentate gyrus and CA3 of the hippocampus. Dentate gyrus is a brain region where adult neurogenesis occurs, and aberrant adult neurogenesis in dentate gyrus has been implicated in major depression disorder. Indeed, Tmem108 mutant mice had lower immobility than wild type mice in tail suspension test and forced swimming test. BrdU and anti-Ki67 antibody staining indicated that adult neurogenesis of the hippocampal dentate gyrus region decreased in Tmem108 mutant mice. qPCR results showed that expression of Axin2, DISC1 and β-Catenin, three dentate gyrus adult neurogenesis related genes in Wnt/β-Catenin signaling pathway, decreased in Tmem108 mutant mice. Furthermore, Tmem108 enhanced free β-Catenin level in dual luciferase assay. Thus, our data suggest that Tmem108 increases adult neurogenesis and plays a complexity role in psychiatric disorders.

Oligodendrocyte (OL) myelination is a critical process for the neuronal axon function in the central nervous system. After demyelination occurs because of pathophysiology, remyelination makes repairs similar to myelination. Proliferation and differentiation are the two main stages in OL myelination, and most factors commonly play converse roles in these two stages, except for a few factors and signaling pathways, such as OLIG2 (Oligodendrocyte transcription factor 2). Moreover, some OL maturation gene mutations induce hypomyelination or hypermyelination without an obvious function in proliferation and differentiation. Herein, three types of factors regulating myelination are reviewed in sequence.

Post-synaptic specialization is critical to the neurotransmitter release and action potential conduction. The neuromuscular junctions (NMJs) are the synapses between the motor neurons and muscle cells and have a more specialized post-synaptic membrane than synapses in the central nervous system (CNS). The sarcolemma within NMJ folded to form some invagination portions called junctional folds (JFs), and they have important roles in maintaining the post-synaptic membrane structure. The NMJ formation and the acetylcholine receptor (AChR) clustering signal pathway have been extensively studied and reviewed. Although it has been suggested that JFs are related to maintaining the safety factor of neurotransmitter release, the formation mechanism and function of JFs are still unclear. This review will focus on the JFs about evolution, formation, function, and disorders. Anticipate understanding of where they are coming from and where we will study in the future.

Whether mature oligodendrocytes (mOLs) participate in remyelination has been disputed for several decades. Recently, some studies have shown that mOLs participate in remyelination by producing new sheaths. However, whether mOLs can produce new oligodendrocytes by asymmetric division has not been proven. Zebrafish is a perfect model to research remyelination compared to other species. In this study, optic nerve crushing did not induce local mOLs death. After optic nerve transplantation from olig2:eGFP fish to AB/WT fish, olig2⁺ cells from the donor settled and rewrapped axons in the recipient. After identifying these rewrapping olig2⁺ cells as mOLs at 3 months posttransplantation, in vivo imaging showed that olig2⁺ cells proliferated. Additionally, in vivo imaging of new olig2⁺ cell division from mOLs was also captured within the retina. Finally, fine visual function was renewed after the remyelination program was completed. In conclusion, our in vivo imaging results showed that new olig2⁺ cells were born from mOLs by asymmetric division in adult zebrafish, which highlights the role of mOLs in the progression of remyelination in the mammalian CNS.

Low-density lipoprotein receptor-related protein 4 (Lrp4) is a critical protein involved in the Agrin-Lrp4-MuSK signaling pathway that drives the clustering of acetylcholine receptors (AChRs) at the neuromuscular junction (NMJ). Many studies have shown that Lrp4 also functions in kidney development, bone formation, nervous system development, etc. However, whether Lrp4 participates in nerve regeneration in mammals remains unknown. Herein, we show that Lrp4 is expressed in SCs and that conditional knockout (cKO) of Lrp4 in SCs promotes peripheral nerve regeneration. In Lrp4 cKO mice, the demyelination of SCs was accelerated, and the proliferation of SCs was increased in the injured nerve. Furthermore, we identified that two myelination-related genes, Krox-20 and Mpz, were downregulated more dramatically in the cKO group than in the control group. Our results elucidate a novel role of Lrp4 in peripheral nerve regeneration and thereby provide a potential therapeutic target for peripheral nerve recovery.