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Prodromal memory deficits represent an important marker for the development of schizophrenia (SZ), in which glutamatergic hypofunction occurs in the prefrontal cortex (PFC). The mGluR2/3 agonist LY379268 (LY37) attenuates excitatory N-methyl-D-aspartate receptor (NMDAR)-induced neurotoxicity, a central pathological characteristic of glutamatergic hypofunction. We therefore hypothesized that early treatment with LY37 would rescue cognitive deficits and confer benefits for SZ-like behaviors in adults. To test this, we assessed whether early intervention with LY37 would improve learning outcomes in the Morris Water Maze for rats prenatally exposed to methylazoxymethanol acetate (MAM), a neurodevelopmental SZ model. We found that a medium dose of LY37 prevents learning deficits in MAM rats. These effects were mediated through postsynaptic mGluR2/3 via improving GluN2B-NMDAR function by inhibiting glycogen synthase kinase-3β (GSK3β). Furthermore, dendritic spine loss and learning and memory deficits observed in adult MAM rats were restored by juvenile LY37 treatment, which did not change prefrontal neuronal excitability and glutamatergic synaptic transmission in adult normal rats. Our results provide a mechanism for mGluR2/3 agonists against NMDAR hypofunction, which may prove to be beneficial in the prophylactic treatment of SZ.
Pubmed ID: 29793154 RIS Download
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Neurolucida is advanced scientific software for brain mapping, neuron reconstruction, anatomical mapping, and morphometry. Since its debut more than 20 years ago, Neurolucida has continued to evolve and has become the worldwide gold-standard for neuron reconstruction and 3D mapping. Neurolucida has the flexibility to handle data in many formats: using live images from digital or video cameras; stored image sets from confocal microscopes, electron microscopes, and scanning tomographic sources, or through the microscope oculars using the patented LucividTM. Neurolucida controls a motorized XYZ stage for integrated navigation through tissue sections, allowing for sophisticated analysis from many fields-of-view. Neurolucidas Serial Section Manager integrates unlimited sections into a single data file, maintaining each section in aligned 3D space for full quantitative analysis. Neurolucidas neuron tracing capabilities include 3D measurement and reconstruction of branching processes. Neurolucida also features sophisticated tools for mapping delineate and map anatomical regions for detailed morphometric analyses. Neurolucida uses advanced computer-controlled microscopy techniques to obtain accurate results and speed your work. Plug-in modules are available for confocal and MRI analysis, 3D solid modeling, and virtual slide creation. The user-friendly interface gives you rapid results, allowing you to acquire data and capture the full 3D extent of neurons and brain regions. You can reconstruct neurons or create 3D serial reconstructions directly from slides or acquired images, and Neurolucida offers full microscope control for brightfield, fluorescent, and confocal microscopes. Its added compatibility with 64-bit Microsoft Vista enables reconstructions with even larger images, image stacks, and virtual slides. Adding the Solid Modeling Module allows you to rotate and view your reconstructions in real time. Neurolucida is available in two separate versions Standard and Workstation. The Standard version enables control of microscope hardware, whereas the Workstation version is used for offline analysis away from the microscope. Neurolucida provides quantitative analysis with results presented in graphical or spreadsheet format exportable to Microsoft Excel. Overall, features include: - Tracing Neurons - Anatomical Mapping - Image Processing and Analysis Features - Editing - Morphometric Analysis - Hardware Integration - Cell Analysis - Visualization Features Sponsors: Neurolucida is supported by MBF Bioscience.
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