Expression of neuregulin and ErbB3 and ErbB4 after a traumatic lesion in the ventral funiculus of the spinal cord and in the intact primary olfactory system.
Neuron-derived neuregulins have been implicated in the regulation of glial cell function and survival. This factor family and its receptors may therefore be assumed to be of importance for the cellular response to traumatic injury. In this study we have examined the distribution of mRNA for neuregulin 1 (NRG1), ErbB3 and ErbB4-receptor tyrosine kinases after a ventral funiculus lesion in the lumbar spinal cord (VFL). The techniques used were in situ hybridization and immunohistochemistry. The survival times were 1-21 days. The spinal cords from normal adult and embryonic rats were used as controls. For comparison, sections from the olfactory bulb of perinatal and adult rats were also included in the study. Expression of NRG1 mRNA was observed in motoneurons in the intact spinal cord. A decrease in the labeling for NRG1 mRNA was seen during the first 5 days after VFL but then became slightly upregulated at 3 weeks after the lesion. A high labeling signal for ErbB3-mRNA was observed in the ventral and dorsal roots of E16 and E18 embryos. Labeling for ErbB3-mRNA was strong in the affected ventral root at 3 days after the VFL, reached a maximum at 1 week and was still upregulated after 3 weeks. Increased labeling for ErbB3 was also noted in scattered cells in the scar tissue 1-3 weeks after the VFL. These findings were verified with immunohistochemistry for ErbB3. A strong labeling for ErbB3 in the olfactory nerve fiber layer and olfactory nerve bundles was observed in rats of all ages examined. ErbB4 had strong expression in the embryonic spinal cord, but no evidence for lesion-induced regulation of ErbB4 receptors could be found after the VFL. Our data show that ErbB3 in the ventral roots was upregulated after a VFL and that NRG1 mRNA was initially downregulated in the motoneurons. The lesion-induced changes in the expression of NRG1 and ErbB3 in the injured spinal cord and denervated ventral root can be assumed to be of importance for axonal growth and the regulation of glial cell survival.
Lindholm
T
T
Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden. tomas.lindholm@neuro.ki.se
Cullheim
S
S
Deckner
M
M
Carlstedt
T
T
Risling
M
M
D000818:Animals; D000831:Animals, Newborn; D004195:Disease Models, Animal; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005455:Fluorescent Antibody Technique; D005786:Gene Expression Regulation / Q000502:physiology; D005911:Gliosis / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D009046:Motor Neurons / Q000378:metabolism* / Q000473:pathology; D009410:Nerve Degeneration / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D009416:Nerve Regeneration / Q000235:genetics*; D020890:Neuregulin-1 / Q000235:genetics / Q000378:metabolism*; D009830:Olfactory Bulb / Q000254:growth & development / Q000293:injuries / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020893:Receptor, ErbB-3 / Q000235:genetics / Q000378:metabolism*; D066247:Receptor, ErbB-4; D013116:Spinal Cord / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D013119:Spinal Cord Injuries / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D013126:Spinal Nerve Roots / Q000293:injuries / Q000473:pathology / Q000503:physiopathology; D015854:Up-Regulation / Q000502:physiology
D020890:Neuregulin-1; D012333:RNA, Messenger; D066246:ErbB Receptors; C587691:Erbb4 protein, rat; D020893:Receptor, ErbB-3; D066247:Receptor, ErbB-4