Abstract
BackgroundTransmembrane 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.ResultsHere 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.ConclusionsThus, our data suggest that Tmem108 increases adult neurogenesis and plays a complexity role in psychiatric disorders.
Highlights
Adult neurogenesis, the generation of functional neurons from adult neural progenitors, mainly occurs in subventricular zone (SVZ) of the lateral ventricle and subgranular zone (SGZ) of the hippocampal dentate gyrus (DG) [1,2,3]
The results showed that Transmembrane protein 108 (Tmem108) played a complexity role in psychiatric disorders, Tmem108 mutant mice had lower immobility than wild type mice in depression-like behavior tests, and adult neurogenesis of the hippocampal DG in Tmem108 mutant mice decreased
We found that Tmem108 had high expression in posteromedial cortical amygdaloid nucleus (PMCo), parafascicular thalamic nucleus (PTN), cortex, DG and CA3 of the hippocampus than other regions in brain coronal section slides (Fig. 1C)
Summary
The generation of functional neurons from adult neural progenitors, mainly occurs in subventricular zone (SVZ) of the lateral ventricle and subgranular zone (SGZ) of the hippocampal dentate gyrus (DG) [1,2,3]. Many molecular pathways involve in adult neurogenesis [4], such as Shh, Notch and Wnt signaling pathway. Wnt/β-Catenin signaling pathway has an important role in promoting proliferation of adult neuronal stem. Aberrant adult neurogenesis in DG has been implicated in major depression disorder (MDD); in addition, enhancement of adult neurogenesis is regarded as one of the efficient indexes to MDD treatment [5, 6]. MDD, according to world health organization statistics in 2017, as a common mental disorder, affected more than 300 million people worldwide [7]. Transmembrane protein 108 (Tmem108), named Retrolinkin [8,9,10], locates on the human chromosome 3q21. Transmembrane protein 108 (Tmem108) is a risk gene of psychiatric diseases including schizophrenia, bipolar disorder and major depression disorder.
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