EphB2 activates CREB-dependent expression of Annexin A1 to regulate dendritic spine morphogenesis

Lin, Yuan; Yi, Wanying; Sun, Cuiyun; Ma, Shuangshuang; Wang, Jiali; Liu, Saijuan; Chen, Yijing; Chen, Yuewen; Chen, Yu

doi:10.1016/j.bbrc.2021.11.011

Cited by 8 publications

(6 citation statements)

References 38 publications

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“…Ephins and their receptors are involved in the pathology of Alzheimer's disease 50 , 51 and depression, 52 and are implicated in the formation and maturation of dendritic spines and synaptic plasticity. 53 , 54 Here we utilized a MIA SZ rat model and reported abnormal expression in the EphB signaling pathway in MIA offspring, including an increase in EphB2 receptors and a reduction in p‐cofilin, an important downstream molecule of EphB signaling. Interestingly, enhanced EphB2, a key regulator of NMDA receptor at synapses, 55 was accompanied with upregulated expression of NMDA receptors but decreased expression of AMPA receptors observed in MIA offspring.…”

Section: Discussionmentioning

confidence: 99%

Impaired erythropoietin‐producing hepatocellular B receptors signaling in the prefrontal cortex and hippocampus following maternal immune activation in male rats

Shao

Cai

Chen

et al. 2023

Genes Brain and Behavior

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An environmental risk factor for schizophrenia (SZ) is maternal infection, which exerts longstanding effects on the neurodevelopment of offspring. Accumulating evidence suggests that synaptic disturbances may contribute to the pathology of the disease, but the underlying molecular mechanisms remain poorly understood. Erythropoietin‐producing hepatocellular B (EphB) receptor signaling plays an important role in synaptic plasticity by regulating the formation and maturation of dendritic spines and regulating excitatory neurotransmission. We examined whether EphB receptors and downstream associated proteins are susceptible to environmental risk factors implicated in the etiology of synaptic disturbances in SZ. Using an established rodent model, which closely imitates the characteristics of SZ, we observed the behavioral performance and synaptic structure of male offspring in adolescence and early adulthood. We then analyzed the expression of EphB receptors and associated proteins in the prefrontal cortex and hippocampus. Maternal immune activation offspring showed significantly progressive cognitive impairment and pre‐pulse inhibition deficits together with an increase in the expression of EphB2 receptors and NMDA receptor subunits. We also found changes in EphB receptor downstream signaling, in particular, a decrease in phospho‐cofilin levels which may explain the reduced dendritic spine density. Besides, we found that the AMPA glutamate, another glutamate ionic receptor associated with cofilin, decreased significantly in maternal immune activation offspring. Thus, alterations in EphB signaling induced by immune activation during pregnancy may underlie disruptions in synaptic plasticity and function in the prefrontal cortex and hippocampus associated with behavioral and cognitive impairment. These findings may provide insight into the mechanisms underlying SZ.

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Section: Discussionmentioning

confidence: 99%

Impaired erythropoietin‐producing hepatocellular B receptors signaling in the prefrontal cortex and hippocampus following maternal immune activation in male rats

Shao

Cai

Chen

et al. 2023

Genes Brain and Behavior

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“…EphB2 is a type of receptor tyrosine kinase that acts as a cell surface receptor and plays a crucial role in a variety of biological processes, especially in the development and regulation of the nervous system. In the adult nervous system, EphB2 is involved in the regulation of synaptic plasticity [32].…”

Section: Relationship Between Neuronal Signaling and The Pathogenesis...mentioning

confidence: 99%

Identification of the Shared Gene Signatures and Molecular Mechanisms Between Polycystic Ovarian Syndrome and Major Depressive Disorder: Evidence From Transcriptome Data

Zheng,

Wang,

Liu

2023

Preprint

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Background: Polycystic Ovarian Syndrome (PCOS) is the most common metabolic and endocrine disorder in reproductive-age women, while Major Depressive Disorder (MDD) is a relatively common psychiatric condition. Previous studies have suggested a potential link between PCOS and MDD, but the underlying pathophysiological mechanisms remain unclear. This study aims to identify differential expression genes (DEGs) between PCOS and MDD using bioinformatics methods, explore the associated molecular mechanisms, elucidate the TF-mRNA-miRNA regulatory network involved, predict potential drug molecules, and validate them through molecular docking. Methods: Microarray datasets GSE34526 and GSE125664 were downloaded from the Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) of PCOS and MDD were analyzed using the GEO2R online tool to obtain shared DEGs to both. Next, the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis for the shared DEGs were performed. Then, protein-protein interaction (PPI) network were constructed and the hub genes were identified using the STRING database and Cytoscape software. Next, NetworkAnalyst was used to construct network between target transcription factors (TFs), microRNAs (miRNAs), and hub genes. Finally, the DSigDB database was used to search for potential drug molecules for the treatment of PCOS combined with MDD, followed by molecular docking using the AutoDock Tools and visualization of the results using PyMol 2.4.0. Results: In the above two datasets, 158 shared DEGs were identified. GO and KEGG enrichment analyses showed that these shared DEGs were mainly enriched in pathways related to neural signaling, energy metabolism, and chronic inflammation with immune dysregulation. In addition, genes with greater than 2-fold median interaction number were further screened by Cytoscape's plugin, cytoNCA, and finally 6 hub genes were selected from the PPI network, ncluding GRIN1, CNR1, DNM1, SYNJ1, PLA2G4A and EPHB2. Then, through the construction of the TF-mRNA-miRNA regulatory network, it was concluded that hsa-miR-27a might be a strongly associated miRNA with the pathogenesis of PCOS and MDD, while TFAP2A might be a strongly associated TF. Finally, orlistat, docosahexaenoic acid (DHA), capsaicin, and myo-inositol were considered as potential drug molecules for the treatment of PCOS combined with MDD using the DSigDB database and related study finding, and then molecular docking was performed using AutoDock Tools. The drug-molecule combination with the lowest binding energy was visualized using PyMol software and it found to be well docked. Conclusions: In summary, we constructed a TF-mRNA-miRNA regulatory network for the first time to characterize the interactions among potential TFs, miRNAs, and hub genes associated with PCOS and MDD, and concluded that aberrant neuronal signaling, disturbed energy metabolism, and immune dysregulation with inflammatory response may be the common pathogenesis of PCOS and MDD. In addition, we identified potential drug molecules for the treatment of PCOS and MDD and performed molecular docking validation. This provides new insights to identify potential associations, potential biomarkers and therapeutic agents for PCOS and MDD.

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“…All spines exhibit dynamic forms, dependent on the received excitatory and inhibitory inputs. The structure of most established spines is recognized according to four morphological categories, critical for normal brain functions: filopodia, stubby, thin, and mushroom ( Figure 2 ), generated separately or by switching from each other in a variety of conditions [ 34 , 35 ].…”

Section: Post-synapses With Spinesmentioning

confidence: 99%

“…The ensuing effects exhibit various levels of distinction [ 52 ]. Spine morphogenesis is largely regulated by actin cytoskeleton and annexin A1 [ 34 , 42 ]. In vivo studies have demonstrated that spines are motile: their plastic structures are influenced by sensory changes [ 51 ]; and their remodeling is established upon a variety of physiological stimuli [ 52 , 53 , 54 ].…”

Section: Post-synapses With Spinesmentioning

confidence: 99%

Post-Synapses in the Brain: Role of Dendritic and Spine Structures

Meldolesi

2022

Biomedicines

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Brain synapses are neuronal structures of the greatest interest. For a long time, however, the knowledge about them was variable, and interest was mostly focused on their pre-synaptic portions, especially neurotransmitter release from axon terminals. In the present review interest is focused on post-synapses, the structures receiving and converting pre-synaptic messages. Upon further modulation, such messages are transferred to dendritic fibers. Dendrites are profoundly different from axons; they are shorter and of variable thickness. Their post-synapses are of two types. Those called flat/intended/aspines, integrated into dendritic fibers, are very frequent in inhibitory neurons. The spines, small and stemming protrusions, connected to dendritic fibers by their necks, are present in almost all excitatory neurons. Several structures and functions including the post-synaptic densities and associated proteins, the nanoscale mechanisms of compartmentalization, the cytoskeletons of actin and microtubules, are analogous in the two post-synaptic forms. However other properties, such as plasticity and its functions of learning and memory, are largely distinct. Several properties of spines, including emersion from dendritic fibers, growth, change in shape and decreases in size up to disappearance, are specific. Spinal heads correspond to largely independent signaling compartments. They are motile, their local signaling is fast, however transport through their thin necks is slow. When single spines are activated separately, their dendritic effects are often lacking; when multiple spines are activated concomitantly, their effects take place. Defects of post-synaptic responses, especially those of spines, take place in various brain diseases. Here alterations affecting symptoms and future therapy are shown to occur in neurodegenerative diseases and autism spectrum disorders.

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EphB2 activates CREB-dependent expression of Annexin A1 to regulate dendritic spine morphogenesis

Cited by 8 publications

References 38 publications

Impaired erythropoietin‐producing hepatocellular B receptors signaling in the prefrontal cortex and hippocampus following maternal immune activation in male rats

Impaired erythropoietin‐producing hepatocellular B receptors signaling in the prefrontal cortex and hippocampus following maternal immune activation in male rats

Identification of the Shared Gene Signatures and Molecular Mechanisms Between Polycystic Ovarian Syndrome and Major Depressive Disorder: Evidence From Transcriptome Data

Post-Synapses in the Brain: Role of Dendritic and Spine Structures

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