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

Abstract

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.

Neuroprotection and immunomodulation following intraspinal axotomy of motoneurons by treatment with adult mesenchymal stem cells

“…Thus, the loss of inputs combined with the close-to-cell-body section of the motor axon triggers degenerative events. Herein, VFC caused death of 67% of the motoneurons, which is in line with previous works [ 4 , 6 , 7 , 32 ]. After ventral root avulsion, in which the motor axons are pulled from the surface of the spinal cord, approximately 80% of motor neurons die within 2 weeks after lesion [ 33 ].…”

Neuregulin-1 Attenuates Neointimal Formation following Vascular Injury and Inhibits the Proliferation of Vascular Smooth Muscle Cells

“…The upregulation of NRG-1 and erbB receptors in the lesion area after injury may also account for the relatively lower concentrations of NRG-1 required in the in vivo studies compared with the amount required to block proliferation in the VSMC cultures. Similarly, the upregulation of NRG-1 and its erbB receptors has also been reported after ischemia and central nervous system injury [31,32,33,34,35,36]. As seen in the vascular injury model, we showed that administration of exogenous NRG-1 was neuroprotective and prevented inflammatory responses caused by ischemia [32, 37].…”

Identification of pivotal genes and pathways for spinal cord injury via bioinformatics analysis

“…In the present study, ERBB4 and CYBA were in the network diagram of 1-month and 2-week post-SCI group vs. control group, and all samples, respectively. Lindholm et al ( 33 ) demonstrated that in the vicinity of the lesion, a number of scattered cells expressed ErbB mRNA following SCI. Neuregulin1/ErbB signaling may be involved in the development of SCI ( 34 ).…”