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Distribution of RET immunoreactivity in the rodent spinal cord and changes after nerve injury
Author(s) -
Jongen Joost L.M.,
Jaarsma Dick,
Hossaini Mehdi,
Natarajan Dipa,
Haasdijk Elize D.,
Holstege Jan C.
Publication year - 2006
Publication title -
journal of comparative neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.855
H-Index - 209
eISSN - 1096-9861
pISSN - 0021-9967
DOI - 10.1002/cne.21234
Subject(s) - axotomy , spinal cord , biology , glial cell line derived neurotrophic factor , anatomy , in situ hybridization , neuroscience , neurotrophic factors , central nervous system , receptor , messenger rna , biochemistry , gene
RET (for “rearranged during transfection”) is a transmembrane tyrosine kinase signaling receptor for members of the glial cell line‐derived neurotrophic factor (GDNF) family of ligands. We used RET immunohistochemistry (IHC), double‐labeling immunofluorescence (IF), and in situ hybridization (ISH) in adult naïve and nerve‐injured rats to study the distribution of RET in the spinal cord. In the dorsal horn, strong RET‐immunoreactive (‐ir) fibers were abundant in lamina II‐inner (II i ), although this labeling was preferentially observed after an antigen‐unmasking procedure. After dorsal rhizotomy, RET‐ir fibers in lamina II i completely disappeared from the dorsal horn, indicating that they were all primary afferents. After peripheral axotomy, RET‐ir in primary afferents decreased in lamina II i and appeared to increase slightly in laminae III and IV. RET‐ir was also observed in neurons and dendrites throughout the dorsal horn. Some RET‐ir neurons in lamina I had the morphological appearance of nociceptive projection neurons, which was confirmed by the finding that 53% of RET‐ir neurons in lamina I colocalized with neurokinin‐1. GDNF‐ir terminals were in close proximity to RET‐ir neurons in the superficial dorsal horn. In the ventral horn, RET‐ir was strongly expressed by motoneurons, with the strongest staining in small, presumably γ‐motoneurons. Increased RET expression following peripheral axotomy was most pronounced in α‐motoneurons. The expression and regulation pattern of RET in the spinal cord are in line with its involvement in regenerative processes following nerve injury. The presence of RET in dorsal horn neurons, including nociceptive projection neurons, suggests that RET also has a role in signal transduction at the spinal level. This role may include mediating the effects of GDNF released from nociceptive afferent fibers. J. Comp. Neurol. 500:1136–1153, 2007. © 2006 Wiley‐Liss, Inc.