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Transplanting embryonic precursors of GABAergic neurons from the medial ganglionic eminence (MGE) into adult mouse spinal cord ameliorates mechanical and thermal hypersensitivity in peripheral nerve injury models of neuropathic pain. Although Fos and transneuronal tracing studies strongly suggest that integration of MGE-derived neurons into host spinal cord circuits underlies recovery of function, the extent to which there is synaptic integration of the transplanted cells has not been established. Here, we used electron microscopic immunocytochemistry to assess directly integration of GFP-expressing MGE-derived neuronal precursors into dorsal horn circuitry in intact, adult mice with short- (5-6 weeks) or long-term (4-6 months) transplants. We detected GFP with pre-embedding avidin-biotin-peroxidase and GABA with post-embedding immunogold labeling. At short and long times post-transplant, we found host-derived synapses on GFP-immunoreactive MGE cells bodies and dendrites. The proportion of dendrites with synaptic input increased from 50% to 80% by 6 months. In all mice, MGE-derived terminals formed synapses with GFP-negative (host) cell bodies and dendrites and, unexpectedly, with some GFP-positive (i.e., MGE-derived) dendrites, possibly reflecting autoapses or cross talk among transplanted neurons. We also observed axoaxonic appositions between MGE and host terminals. Immunogold labeling for GABA confirmed that the transplanted cells were GABAergic and that some transplanted cells received an inhibitory GABAergic input. We conclude that transplanted MGE neurons retain their GABAergic phenotype and integrate dynamically into host-transplant synaptic circuits. Taken together with our previous electrophysiological analyses, we conclude that MGE cells are not GABA pumps, but alleviate pain and itch through synaptic release of GABA.
Pubmed ID: 29134656 RIS Download
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This unknown targets GABA
View all literature mentionsThis polyclonal targets GFP
View all literature mentionsThis monoclonal targets GABA
View all literature mentionsPlatform for exploring spinal cord at cellular and molecular levels. Map of gene expression for adult and juvenile mouse spinal cord. Provides map of normal mouse when used to compare gene expression in diseased or injury models. Interactive database of gene expression mapped across all anatomic segments of mouse spinal cord at postnatal days 4 and 56. Indexed set of images based on RNA in situ hybridization data, searchable and sortable by gene, age, expression, cervical, thoracic, lumbar, sacral, and coccygeal segments.
View all literature mentionsA portal into the 3D ultrastructure of the brain providing: Anatomy of astrocytes, axons, dendrites, hippocampus, organelles, synapses; procedures of 3D reconstruction and tissue preparation; as well as an atlas of ultrastructural neurocytology (by Josef Spacek), online aligned images, and reconstructed dendrites. Synapse Web hosts an ultrastructural atlas containing more than 500 electron micrographs (added to regularly) that identify unique ultrastructural and cellular components throughout the brain. Additionally, Synapse Web has raw images, reconstructions, and quantitative data along with tutorial instructions and numerous tools for investigating the functional structure of objects that have been serial thin sectioned for electron microscopy.
View all literature mentionsThis is the website of the Structural Brain Mapping Group at the Department of Psychiatry, University of Jena. Our principal research focuses on the development of methods for structural brain imaging and their application. Specific areas of interest include the investigation of structural brain plasticity and schizophrenia research. Regional structural brain changes are among the most robust biological findings in schizophrenia, yet the underlying pathophysiological changes remain poorly understood. Recent evidence suggests that abnormal neuronal/dendritic plasticity is related to alterations in membrane lipids. We examined whether serum activity of membrane lipid remodeling/repairing cytosolic phospholipase A2 (PLA2) were related to regional brain structure in magnetic resonance images (MRI). The study involved 24 schizophrenia patients, who were either drug-nave or off antipsychotic medication, and 25 healthy controls. Using voxel-based morphometry (VBM) analysis of T1-high-resolution MRI-images, we correlated both gray matter and white matter changes with serum PLA2-activity. PLA2 activity was increased in patients, consistent with previous findings. VBM group comparison of patients vs. controls showed abnormalities of frontal and medial temporal cortices/hippocampus, and left middle/superior temporal gyrus in first-episode patients. Group comparison of VBM/ PLA2-correlations revealed a distinct pattern of disease-related interactions between gray/white matter changes in patients and PLA2-activity: in first-episode patients (n = 13), PLA2-activity was associated with structural alterations in the left prefrontal cortex and the bilateral thalamus. Recurrent-episode patients (n = 11) showed a wide-spread pattern of associations between PLA2-activity and structural changes in the left (less right) prefrontal and inferior parietal cortex, the left (less right) thalamus and caudate nucleus, the left medial temporal and orbitofrontal cortex and anterior cingulum, and the cerebellum. Our findings demonstrate a potential association between membrane lipid biochemistry and focal brain structural abnormalities in schizophrenia. Differential patterns in first-episode vs. chronic patients might be related to PLA2-increase at disease-onset reflecting localized regenerative activity, whereas correlations in recurrent- episode patients might point to less specific neurodegenerative aspects of disease progression.
View all literature mentionsAn organization of transplant professionals dedicated to advancing the field of transplantation and improving patient care by promoting research, education, advocacy, and organ donation.
View all literature mentionsThis unknown targets GABA
View all literature mentionsThis unknown targets GABA
View all literature mentionsThis polyclonal targets GFP
View all literature mentionsThis is the website of the Structural Brain Mapping Group at the Department of Psychiatry, University of Jena. Our principal research focuses on the development of methods for structural brain imaging and their application. Specific areas of interest include the investigation of structural brain plasticity and schizophrenia research. Regional structural brain changes are among the most robust biological findings in schizophrenia, yet the underlying pathophysiological changes remain poorly understood. Recent evidence suggests that abnormal neuronal/dendritic plasticity is related to alterations in membrane lipids. We examined whether serum activity of membrane lipid remodeling/repairing cytosolic phospholipase A2 (PLA2) were related to regional brain structure in magnetic resonance images (MRI). The study involved 24 schizophrenia patients, who were either drug-nave or off antipsychotic medication, and 25 healthy controls. Using voxel-based morphometry (VBM) analysis of T1-high-resolution MRI-images, we correlated both gray matter and white matter changes with serum PLA2-activity. PLA2 activity was increased in patients, consistent with previous findings. VBM group comparison of patients vs. controls showed abnormalities of frontal and medial temporal cortices/hippocampus, and left middle/superior temporal gyrus in first-episode patients. Group comparison of VBM/ PLA2-correlations revealed a distinct pattern of disease-related interactions between gray/white matter changes in patients and PLA2-activity: in first-episode patients (n = 13), PLA2-activity was associated with structural alterations in the left prefrontal cortex and the bilateral thalamus. Recurrent-episode patients (n = 11) showed a wide-spread pattern of associations between PLA2-activity and structural changes in the left (less right) prefrontal and inferior parietal cortex, the left (less right) thalamus and caudate nucleus, the left medial temporal and orbitofrontal cortex and anterior cingulum, and the cerebellum. Our findings demonstrate a potential association between membrane lipid biochemistry and focal brain structural abnormalities in schizophrenia. Differential patterns in first-episode vs. chronic patients might be related to PLA2-increase at disease-onset reflecting localized regenerative activity, whereas correlations in recurrent- episode patients might point to less specific neurodegenerative aspects of disease progression.
View all literature mentionsThis monoclonal targets GABA
View all literature mentionsPlatform for exploring spinal cord at cellular and molecular levels. Map of gene expression for adult and juvenile mouse spinal cord. Provides map of normal mouse when used to compare gene expression in diseased or injury models. Interactive database of gene expression mapped across all anatomic segments of mouse spinal cord at postnatal days 4 and 56. Indexed set of images based on RNA in situ hybridization data, searchable and sortable by gene, age, expression, cervical, thoracic, lumbar, sacral, and coccygeal segments.
View all literature mentionsAn organization of transplant professionals dedicated to advancing the field of transplantation and improving patient care by promoting research, education, advocacy, and organ donation.
View all literature mentionsThis polyclonal targets GFP
View all literature mentionsA portal into the 3D ultrastructure of the brain providing: Anatomy of astrocytes, axons, dendrites, hippocampus, organelles, synapses; procedures of 3D reconstruction and tissue preparation; as well as an atlas of ultrastructural neurocytology (by Josef Spacek), online aligned images, and reconstructed dendrites. Synapse Web hosts an ultrastructural atlas containing more than 500 electron micrographs (added to regularly) that identify unique ultrastructural and cellular components throughout the brain. Additionally, Synapse Web has raw images, reconstructions, and quantitative data along with tutorial instructions and numerous tools for investigating the functional structure of objects that have been serial thin sectioned for electron microscopy.
View all literature mentionsThe SciCrunch Infrastructure was developed as a cooperative data platform to be used by diverse communities in making data more FAIR.
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