Activation of EphB receptors by ephrinB (efnB) ligands on neuronal cell surface regulates important functions, including neurite outgrowth, axonal guidance, and synaptic plasticity. Here, we show that efnB rescues primary cortical neuronal cultures from necrotic cell death induced by glutamate excitotoxicity and that this function depends on EphB receptors. Importantly, the neuroprotective function of the efnB/EphB system depends on presenilin 1 (PS1), a protein that plays crucial roles in Alzheimer's disease (AD) neurodegeneration. Furthermore, absence of one PS1 allele results in significantly decreased neuroprotection, indicating that both PS1 alleles are necessary for full expression of the neuroprotective activity of the efnB/EphB system. We also show that the ability of brain-derived neurotrophic factor (BDNF) to protect neuronal cultures from glutamate-induced cell death depends on PS1. Neuroprotective functions of both efnB and BDNF, however, were independent of γ-secretase activity. Absence of PS1 decreases cell surface expression of neuronal TrkB and EphB2 without affecting total cellular levels of the receptors. Furthermore, PS1-knockout neurons show defective ligand-dependent internalization and decreased ligand-induced degradation of TrkB and Eph receptors. Our data show that PS1 mediates the neuroprotective activities of efnB and BDNF against excitotoxicity and regulates surface expression and ligand-induced metabolism of their cognate receptors. Together, our observations indicate that PS1 promotes neuronal survival by regulating neuroprotective functions of ligand-receptor systems. 相似文献
European Archives of Psychiatry and Clinical Neuroscience - Previous studies have demonstrated the efficacy of metacognitive training (MCT) in schizophrenia. However, the underlying mechanisms... 相似文献
Decreased gray matter volume (GMV) in the superior temporal gyrus (STG) has been implicated in the neurophysiology of schizophrenia. However, it remains unclear whether volumetric reduction in the subregions of the STG can predict treatment efficacy for schizophrenia. Our cohort included 44 drug-naive, first-episode patients, 42 unaffected siblings and 44 healthy controls. Voxel-based morphometry and pattern classification were utilized to analyze the acquired imaging data as per the anatomical subdivision by a well-defined brainnetome atlas. The patients presented lower GMV values in left TE1.0/1.2 (TE, anterior temporal visual association area) than the siblings, and lower GMV values in the left/right TE1.0/1.2 and left A22r (rostral area 22) than the controls. A positive correlation is observed between the GMV values in the right A38l (lateral area 38) and baseline Positive and Negative Syndrome Scale (PANSS) total scores in the patients. Support vector regression (SVR) results exhibited a significant association between predicted (based on the GMV values in the right A38l) and actual symptomatic improvement based on the reduction ratio of the PANSS total scores (r = 0.498, p = 0.001). Our results suggest that normal structure in the right A38l of the STG may be an important factor indicative of the effects of antipsychotic drugs, which can be potentially used to monitor drug effects for first-episode patients at an early stage in clinical practice.
