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.

Introduction: Contrast-induced spinal cord injury (CIS) is an uncommon yet severe neurological complication following cerebral angiography. It can lead to dire consequences, including limb paralysis, respiratory distress, and even death. Patient concerns: After undergoing cerebral angiography, a 41-year-old male initially displayed symptoms of dizziness and blurred vision, which advanced into dysphoria and limb weakness within 3 hours. These initial symptoms diminished by the 12th hour. Yet, 18 hours following the procedure, the patient developed quadriplegia and paresthesia below the T5 level, even though his deep sensory functions persisted unaffected. Diagnosis: The magnetic resonance imaging and diffusion weighted imaging scans excluded the presence of cerebrovascular ischemia or subarachnoid hemorrhage. However, the magnetic resonance angiography displayed arterial vasospasms in both posterior cerebral arteries and the V4 segment of the right vertebral artery. The encephalopathy symptoms faded within 12 hours, suggesting a probable contrast-induced encephalopathy diagnosis. An magnetic resonance imaging on day 4 revealed an intensified signal in the spinal cord from C1 to T1. This finding supported the diagnosis of CIS. Interventions: Following treatment with mannitol, methylprednisolone, and nimodipine, the patient’s contrast-induced encephalopathy symptoms resolved completely within 12 hours. With a 2-week regimen of aspirin, methylprednisolone, and rehabilitative training, the neurological symptoms from CIS showed steady improvement. Outcomes: The symptoms and signs of CIS gradually improved after 2 weeks’ treatment and rehabilitation program. Conclusion: Given the grave outcomes of CIS, like limb paralysis, breathing difficulties, and even fatality, it is imperative to remain cautious about this complication, even with the use of modern, less harmful contrast agents.

Experimental Autoimmune Myasthenia Gravis (EAMG) remains a cornerstone platform for mechanistic studies of pathogenic antibodies in myasthenia gravis (MG). In particular, monoclonal antibody passive-transfer EAMG (mAb-PTMG) has been instrumental in establishing causal links between defined antibody specificities and downstream neuromuscular junction (NMJ) dysfunction, as well as in dissecting key mechanisms underlying AChR antibody-mediated disease. More recently, PTMG studies using patient-derived MuSK monoclonal antibodies have expanded the mechanistic landscape of MG and provided an in vivo framework for evaluating the efficacy and mechanisms of action of agonistic anti-MuSK therapeutic antibodies. In this review, we summarize practical considerations for monoclonal antibody sourcing and preparation, standardized experimental workflows, major readouts and their interpretation, and representative applications across MG subtypes. We also highlight emerging opportunities for model refinement and translational application, with the aim of supporting mechanism-guided interpretation and the development of targeted antibody therapies.

Postictal depression is a common comorbidity in epilepsy, yet effective treatments remain limited. While ketamine is well-known for its antidepressant properties, its role in postictal depression has not been thoroughly investigated. In this study, we utilized a pilocarpine-induced status epilepticus (SE) mouse model and found that depression-like behavior does not appear within a day after SE but develops within one week and persists for over two weeks. We also observed a significant reduction in hippocampal LRP4 expression one day after SE. However, despite partial recovery over the next seven days, LRP4 levels remained markedly lower through day 14, correlating with the onset and persistence of postictal depression. These findings suggest that SE-induced modulation of LRP4 expression plays distinct roles at different stages of postictal depression. Furthermore, treatment with (2R, 6R)-hydroxynorketamine ((2R, 6R)-HNK), a ketamine metabolite that lacks dissociative and addictive properties while retaining strong antidepressant-like effects, significantly alleviated depressive-like behaviors and reduced LRP4 expression in hippocampal astrocytes within one day of administration. This treatment continued to alleviate depressive-like behaviors for up to seven days, while notably increasing Lrp4 levels within one week. To further investigate the role of LRP4, we generated astrocyte-specific LRP4 overexpression mice by stereotactically injecting an Lrp4 OE adenovirus with the gfaABC1D promoter, driving astrocyte-specific expression, into the molecular layer (ML) of the hippocampus. LRP4 overexpression in hippocampal astrocytes accelerated the onset of depressive-like behaviors and abolished the antidepressant effects of (2R, 6R)-HNK. These findings indicate that (2R, 6R)-HNK alleviates postictal depression induced by pilocarpine through stage-specific modulation of LRP4 expression in hippocampal astrocytes. This research provides novel insights into potential therapeutic targets for managing postictal depression.