Expression of mRNAs for neurotrophin receptors in the dorsal root ganglion and spinal cord during development and following peripheral or central axotomy.
Expression of mRNAs for the protein tyrosine kinases trk, trkB and trkC, encoding essential components of high-affinity neurotrophin receptors, was studied in the spinal cord and dorsal root ganglion during normal development and in the adult rat following peripheral and central axon injury. Northern blots revealed multiple trkB transcripts in the embryonic, early postnatal and adult spinal cord with different patterns of expression during development. The levels of 9.0 kb and 4.8 kb trkB transcripts, encoding a full-length trkB receptor, increased progressively during embryonic development with maximal levels around birth, followed by a decline at adulthood. In contrast, the level of 7.5/7.0 kb trkB transcripts, encoding a truncated trkB receptor, reached maximal levels shortly after birth and similar levels remained in the adult animal. In the spinal cord a 4.7kb trkC transcript was detected with maximal levels shortly after birth. In situ hybridization revealed a uniform labeling throughout the spinal cord for both trkB and trkC mRNAs with maximal intensities of labeling shortly after birth. The level of the 2.4 kb trkB transcript in the spinal cord increased 5-fold 8 days after a crush lesion of the sciatic nerve or the dorsal root, while no change was seen in the levels of the other trkB transcripts. No change in the 4.7 kb trkC mRNA was seen following these two injuries, although increased levels of several smaller size trkC transcripts were observed. For both trkB and trkC, similar size transcripts as seen in the spinal cord were also detected in adult rat dorsal root ganglia. Consistent with previous observations of decreased levels of cytoskeletal proteins after peripheral and central axotomy, the level of neurofilment light chain mRNA decreased markedly in the dorsal root ganglia following a crush lesion of the sciatic nerve or of the dorsal root. A small decrease was also seen in the level of preprotachykinin-A mRNA encoding the protein precursor of substance P. In the same animals, the levels of all five trkB transcripts increased 3-fold in the dorsal root ganglia in response to these two injuries. A small increase was also seen in the level of trkC mRNA. The level of brain-derived neurotrophic factor (BDNF) mRNA increased two-fold in the dorsal root ganglia following either of the two lesions, while no change was detected in trk mRNA following these two injuries.(ABSTRACT TRUNCATED AT 400 WORDS)
Department of Medical Chemistry, Karolinska Institutet, Stockholm, Sweden.
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P
Ernfors
C M
CM
Rosario
J P
JP
Merlio
G
G
Grant
H
H
Aldskogius
H
H
Persson
D000818:Animals; D001369:Axons / Q000502:physiology*; D015152:Blotting, Northern; D005727:Ganglia, Spinal / Q000196:embryology / Q000254:growth & development / Q000378:metabolism*; D017403:In Situ Hybridization; D009409:Nerve Crush; D010525:Peripheral Nerves / Q000502:physiology*; D011505:Protein-Tyrosine Kinases / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017475:Receptors, Nerve Growth Factor / Q000235:genetics*; D012584:Sciatic Nerve / Q000378:metabolism; D013116:Spinal Cord / Q000196:embryology / Q000254:growth & development / Q000378:metabolism*; D013126:Spinal Nerve Roots / Q000378:metabolism
D012333:RNA, Messenger; D017475:Receptors, Nerve Growth Factor; D011505:Protein-Tyrosine Kinases