Disabled-1 dorsal horn spinal cord neurons co-express Lmx1b and function in nociceptive circuits
| Autor: | Griselda M. Yvone, Megumi Hirose-Ikeda, Austin Wang, Carmine L. Chavez‐Martinez, Joe C. Udeochu, Patricia E. Phelps, Hannah H. Zhao-Fleming |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Nociception Cell Adhesion Molecules Neuronal Central nervous system LIM-Homeodomain Proteins Nerve Tissue Proteins Article 03 medical and health sciences Glutamatergic Mice 0302 clinical medicine medicine Animals Reelin Extracellular Matrix Proteins biology General Neuroscience Serine Endopeptidases Spinal cord DAB1 Posterior Horn Cells Reelin Protein 030104 developmental biology medicine.anatomical_structure nervous system biology.protein Neuron Nucleus Neuroscience 030217 neurology & neurosurgery Transcription Factors |
| Zdroj: | The European journal of neuroscience. 45(5) |
| ISSN: | 1460-9568 |
| Popis: | The Reelin-signaling pathway is essential for correct neuronal positioning within the central nervous system. Mutant mice with a deletion of Reelin, its lipoprotein receptors, or its intracellular adaptor protein Disabled-1 (Dab1), exhibit nociceptive abnormalities: thermal (heat) hyperalgesia and reduced mechanical sensitivity. To determine dorsal horn alterations associated with these nociceptive abnormalities, we first characterized the correctly positioned Dab1 neurons in wild-type and mispositioned neurons in Reelin-signaling pathway mutant lumbar spinal cord. Using immunofluorescence, we found that 70% of the numerous Dab1 neurons in Reln+/+ laminae I–II and 67% of those in the lateral reticulated area and lateral spinal nucleus co-express the LIM-homeobox transcription factor 1 beta (Lmx1b), an excitatory glutamatergic neuron marker. Evidence of Dab1- and Dab1-Lmx1b neuronal positioning errors was found within the isolectin B4 terminal region of Reln−/− lamina IIinner and in the lateral reticulated area and lateral spinal nucleus, where about 50% of the Dab1-Lmx1b neurons are missing. Importantly, Dab1-Lmx1b neurons in laminae I–II and the lateral reticulated area express Fos after noxious thermal or mechanical stimulation and thus participate in these circuits. In another pain relevant locus – the lateral cervical nucleus, we also found about a 50% loss of Dab1-Lmx1b neurons in Reln−/− mice. We suggest that extensively mispositioned Dab1 projection neurons in the lateral reticulated area, lateral spinal nucleus, and lateral cervical nucleus and the more subtle positioning errors of Dab1 interneurons in laminae I–II contribute to the abnormalities in pain responses found in Reelin-signaling pathway mutants. |
| Databáze: | OpenAIRE |
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