Disabled-1 dorsal horn spinal cord neurons co-express Lmx1b and function in nociceptive circuits.

Autor: Yvone GM; Department of Integrative Biology and Physiology, UCLA, Terasaki Life Sciences Building, 610 Charles Young Dr. E, Los Angeles, CA, 90095-7239, USA., Zhao-Fleming HH; Department of Integrative Biology and Physiology, UCLA, Terasaki Life Sciences Building, 610 Charles Young Dr. E, Los Angeles, CA, 90095-7239, USA., Udeochu JC; Department of Integrative Biology and Physiology, UCLA, Terasaki Life Sciences Building, 610 Charles Young Dr. E, Los Angeles, CA, 90095-7239, USA., Chavez-Martinez CL; Department of Integrative Biology and Physiology, UCLA, Terasaki Life Sciences Building, 610 Charles Young Dr. E, Los Angeles, CA, 90095-7239, USA., Wang A; Department of Integrative Biology and Physiology, UCLA, Terasaki Life Sciences Building, 610 Charles Young Dr. E, Los Angeles, CA, 90095-7239, USA., Hirose-Ikeda M; Department of Integrative Biology and Physiology, UCLA, Terasaki Life Sciences Building, 610 Charles Young Dr. E, Los Angeles, CA, 90095-7239, USA., Phelps PE; Department of Integrative Biology and Physiology, UCLA, Terasaki Life Sciences Building, 610 Charles Young Dr. E, Los Angeles, CA, 90095-7239, USA.
Jazyk: angličtina
Zdroj: The European journal of neuroscience [Eur J Neurosci] 2017 Mar; Vol. 45 (5), pp. 733-747. Date of Electronic Publication: 2017 Feb 10.
DOI: 10.1111/ejn.13520
Abstrakt: 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 (LSN) 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 LSN, 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 (LCN), 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, LSN, and LCN 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.
(© 2017 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)
Databáze: MEDLINE
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