ABSTRACT
Abstract@#Alzheimer's disease (AD) is a neurodegenerative disease characterized by deposition of β-amyloid (Aβ). Liver X receptors (LXRs), a member of the nuclear receptor transcription factor superfamily, are widely expressed in brain, which may be involved in the development and progression of AD. Based on the international and national publications pertaining to the association between LXRs and AD from 2010 to 2022, this review summarizes the advances on the involvement of LXRs in the regulation of cholesterol metabolism, inflammatory response and synapse formation in the pathogenesis of AD was reviewed, so as to provide insights into the prevention and treatment of AD.
ABSTRACT
Objective • To investigate the signalling pathways mediated by synaptic cell adhesion molecules (sCAMs) in the process of human prenatal synapse formation. Methods • The single-cell RNA-sequencing dataset of prenatal human prefrontal cortex was downloaded from GEO (Gene Expression Omnibus) database. The gene expression dynamics was modelled with pseudotime ordering approach and the protein-protein interaction (PPI) network was constructed by utilizing gene co-expression analysis and PPI database. The interacting molecules and associated pathways of sCAMs were explored. Results • The gene expression dynamics of early synapse formation in excitatory neurons can be modelled with linear trajectory. PPI network analysis identified the interacting molecules of neurexins, neuroligins, and LAR-type receptor-type protein tyrosine phosphatases (LAR-type RPTPs). Guanine nucleotide exchange factor 9 (ARHGEF9) interacted with neurexins and neuroligins, while cell division cycle 42 (CDC42) was the hub of the network. Amyloid precursor protein (APP) interacted with neuroligins and leucine-rich repeat transmembrane neuronal protein 3 (LRRTM3), which is a ligand of neurexins. Finally, mitogen-activated protein kinase 8 (MAPK8), dual specificity phosphatase 4 (DUSP4), and CDC42, which participate MAPK signalling pathways, were involved in the PPI network of protein tyrosine phosphatase receptor type D (PTPRD, a member of LAR-type RPTPs) and its ligands leucine rich repeat and fibronectin type III domain containing 1 (LRFN1), LRFN2, and LRFN5. Conclusion • Interacting proteins and associated pathways of neurexins, neuroligins, and LAR-type RPTPs can be predicted with bioinformatics methods, which may provide insights in experimental studies.
ABSTRACT
Neuroligins (NLs) are postsynaptic cell-adhesion proteins that play important roles in synapse formation and the excitatory-inhibitory balance. They have been associated with autism in both human genetic and animal model studies, and affect synaptic connections and synaptic plasticity in several brain regions. Yet current research mainly focuses on pyramidal neurons, while the function of NLs in interneurons remains to be understood. To explore the functional difference among NLs in the subtype-specific synapse formation of both pyramidal neurons and interneurons, we performed viral-mediated shRNA knockdown of NLs in cultured rat cortical neurons and examined the synapses in the two major types of neurons. Our results showed that in both types of neurons, NL1 and NL3 were involved in excitatory synapse formation, and NL2 in GABAergic synapse formation. Interestingly, NL1 affected GABAergic synapse formation more specifically than NL3, and NL2 affected excitatory synapse density preferentially in pyramidal neurons. In summary, our results demonstrated that different NLs play distinct roles in regulating the development and balance of excitatory and inhibitory synapses in pyramidal neurons and interneurons.
Subject(s)
Animals , Cell Adhesion Molecules, Neuronal , Physiology , Cells, Cultured , Cerebral Cortex , Embryology , Physiology , GABAergic Neurons , Physiology , Interneurons , Physiology , Membrane Proteins , Physiology , Nerve Tissue Proteins , Physiology , Protein Isoforms , Physiology , Pyramidal Cells , Physiology , Rats, Sprague-Dawley , Synapses , PhysiologyABSTRACT
OBJECTIVE To investigate the effects and its underlying mechanis m of bisphenol-A (BPA)exposure on spine and synapse formation in detate gyrus (DG)area of hippoca mpus during criti-cal develop mental period.METHODS Sprague-Dawley(SD)rats were injected intraperitoneally with BPA (50,250 and 500 μg·kg -1·d -1 )fro m postnatal day 7 (PND7)to PND14.Dendritic spine morphol-ogy in DG area was exa mined using Golgi-Cox staining method and determined with I mage J software. Western blotting method was e mployed to test the Wnt related proteins.RESULTS The spine density and the average spine head size in BPA exposed groups significantly decreased in a dose-dependent manner when co mpared to control group(P<0.05).Meanwhile,Wnt related proteins were affected dur-ing BPA exposure.Specifically,the percentage of phosphorylated β-catenin increased following BPA ex-posure (P<0.05),whereas Wnt7a expression level was significantly decreased and Wnt5a expression level increased (P<0.05).CONCLUSION Wnt signaling pathway plays an i mportant role in BPA-in-duced i mpairments in spine and synapse formation.