Cognitive and mood impairments are common central nervous system complications of type 2 diabetes, although the neuronal mechanism(s) remains elusive. Previous studies focused mainly on neuronal inputs such as altered synaptic plasticity. Axon initial segment (AIS) is a specialized functional domain within neurons that regulates neuronal outputs. Structural changes of AIS have been implicated as a key pathophysiological event in various psychiatric and neurological disorders. Here we evaluated the structural integrity of the AIS in brains of db/db mice, an established animal model of type 2 diabetes associated with cognitive and mood impairments. We assessed the AIS before (5 weeks of age) and after (10 weeks) the development of type 2 diabetes, and after daily exercise treatment of diabetic condition. We found that the development of type 2 diabetes is associated with significant AIS shortening in both medial prefrontal cortex and hippocampus, as evident by immunostaining of the AIS structural protein βIV spectrin. AIS shortening occurs in the absence of altered neuronal and AIS protein levels. We found no change in nodes of Ranvier, another neuronal functional domain sharing a molecular organization similar to the AIS. This is the first study to identify AIS alteration in type 2 diabetes condition. Since AIS shortening is known to lower neuronal excitability, our results may provide a new avenue for understanding and treating cognitive and mood impairments in type 2 diabetes.
Pubmed ID: 29937715 RIS Download
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Commercial antibody supplier and developer for biomedical research. These products are compatible with use in flow cytometry and mass cytometry, immunoprecipitation and chip, western blotting, immunofluorescence microscopy, and quantitative multiplexing.
View all literature mentionsA national mouse monoclonal antibody generating resource for biochemical and immunohistochemical applications in mammalian brain. NeuroMabs are generated from mice immunized with synthetic and recombinant immunogens corresponding to components of the neuronal proteome as predicted from genomic and other large-scale cloning efforts. Comprehensive biochemical and immunohistochemical analyses of human, primate and non-primate mammalian brain are incorporated into the initial NeuroMab screening procedure. This yields a subset of mouse mAbs that are optimized for use in brain (i.e. NeuroMabs): for immunocytochemical-based imaging studies of protein localization in adult, developing and pathological brain samples, for biochemical analyses of subunit composition and post-translational modifications of native brain proteins, and for proteomic analyses of native brain protein networks. The NeuroMab facility was initially funded with a five-year U24 cooperative grant from NINDS and NIMH. The initial goal of the facility for this funding period is to generate a library of novel NeuroMabs against neuronal proteins, initially focusing on membrane proteins (receptors/channels/transporters), synaptic proteins, other neuronal signaling molecules, and proteins with established links to disease states. The scope of the facility was expanded with supplements from the NIH Blueprint for Neuroscience Research to include neurodevelopmental targets, the NIH Roadmap for Medical Research to include epigenetics targets, and NIH Office of Rare Diseases Research to include rare disease targets. These NeuroMabs will then be produced on a large scale and made available to the neuroscience research community on an inexpensive basis as tissue culture supernatants or purified immunoglobulin by Antibodies Inc. The UC Davis/NIH NeuroMab Facility makes NeuroMabs available directly to end users and is unable to accommodate sales to distributors for third party distribution. Note, NeuroMab antibodies are now offered through antibodiesinc.
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View all literature mentionsTHIS RESOURCE IS NO LONGER IN SERVICE. Documented on May 5,2022.Tool that predicts interactions between transcription factors and their regulated genes from binding motifs. Understanding vertebrate development requires unraveling the cis-regulatory architecture of gene regulation. PRISM provides accurate genome-wide computational predictions of transcription factor binding sites for the human and mouse genomes, and integrates the predictions with GREAT to provide functional biological context. Together, accurate computational binding site prediction and GREAT produce for each transcription factor: 1. putative binding sites, 2. putative target genes, 3. putative biological roles of the transcription factor, and 4. putative cis-regulatory elements through which the factor regulates each target in each functional role.
View all literature mentionsThis unknown targets Human/Mouse/Rat Neurofascin Affinity Purified Ab
View all literature mentionsThis polyclonal targets Cleaved Caspase-3 (Asp175)
View all literature mentionsThis polyclonal targets SD domain of beta IV spectrin
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View all literature mentionsThis monoclonal targets GAPDH
View all literature mentionsThis monoclonal targets Myelin Basic Protein
View all literature mentionsThis monoclonal targets Ankyrin-G (Staining)
View all literature mentionsTHIS RESOURCE IS NO LONGER IN SERVICE. Documented on April 12,2023. Matlab code for two-factor (location and year) analysis-of-variance model for the calculation of climate anomalies, in which the reference interval is specified as the full length of the dataset. This scheme avoids the affects of shorter (e.g. 1961-1990) reference intervals on the temporal evolution of the spatial standard deviation of climate anomalies. Data files provided.
View all literature mentionsUser interface software for Carl Zeiss light microscopy imaging systems. ZEN is the universal user interface you will see on every imaging system from ZEISS. After selecting fluorophore, ZEN applies the necessary settings to collect and organize data.
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Mus musculus with name BKS.Cg-Dock7m +/+ Lepr
This unknown targets Human/Mouse/Rat Neurofascin Affinity Purified Ab
View all literature mentionsThis polyclonal targets Cleaved Caspase-3 (Asp175)
View all literature mentionsThis polyclonal targets SD domain of beta IV spectrin
View all literature mentionsThis polyclonal targets Rat Caspr
View all literature mentionsThis monoclonal targets GAPDH
View all literature mentionsThis monoclonal targets Myelin Basic Protein
View all literature mentionsThis monoclonal targets Ankyrin-G (Staining)
View all literature mentions
Mus musculus with name BKS.Cg-Dock7m +/+ Lepr
This unknown targets Human/Mouse/Rat Neurofascin Affinity Purified Ab
View all literature mentionsThis polyclonal targets Cleaved Caspase-3 (Asp175)
View all literature mentionsThis polyclonal targets SD domain of beta IV spectrin
View all literature mentionsThis polyclonal targets Rat Caspr
View all literature mentionsThis monoclonal targets GAPDH
View all literature mentionsThis monoclonal targets Myelin Basic Protein
View all literature mentionsThis monoclonal targets Ankyrin-G (Staining)
View all literature mentions
Mus musculus with name BKS.Cg-Dock7m +/+ Lepr