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1.
Neurotrophin expression by spinal motoneurons in adult and developing rats   总被引:4,自引:0,他引:4  
Expression of the neurotrophins NT-4, brain-derived neurotrophic factor (BDNF), and NT-3 in adult rat lumbosacral spinal cord motoneurons is reported. A sensitive in situ hybridization procedure demonstrates localization of the mRNA for each of these neurotrophins within spinal motoneurons of the adult and in early postnatal development. A majority of adult rat spinal cord lumbar motoneurons (approximately 63%) express NT-4 mRNA as assessed by counting motoneurons in the L4 and L5 segments of two adult rat spinal cords on adjacent cresyl violet-stained and in situ hybridization sections. Similarly, a majority of lumbar motoneurons (approximately 73%) express BDNF mRNA. Further analyses of adjacent lumbar spinal cord sections revealed that many, although not all motoneurons coexpress both NT-4 and BDNF mRNAs. At birth, the mRNA encoding NT-3 is expressed in motoneurons, but BDNF mRNA is not apparent until postnatal day 5 (P5) and NT-4 mRNA first appears at P9. The potential biological significance of neurotrophin mRNA expression in spinal motoneurons is supported by immunohistochemical localization of each neurotrophin protein in adult motoneurons. We discuss the potential role of spinal cord neurotrophins as autocrine or paracrine factors involved in modulating motoneuron synaptic function.  相似文献   

2.
We have evaluated changes in the expression of neurotrophin-3 (NT-3) and its tyrosine kinase C (TrkC) receptor in the neuromuscular system as a result of voluntary physical activity. We assessed changes in the mRNAs and proteins for NT-3 and TrkC in the lumbar spinal cord and associated soleus muscle following 3 and 7 days of voluntary wheel running. We used quantitative Taqman RT-PCR to measure mRNA and ELISA to assess protein levels. NT-3 mRNA and protein levels increased in the spinal cord to reach statistical significance after 7 days of exercise compared to sedentary control rats. Immunohistochemical analyses localized the elevated NT-3 to the substantia gelatinosa (SG) and nucleus of the dorsal horn. TrkC mRNA levels were significantly elevated in the spinal cord after 3 and 7 days of running. In the soleus muscle, NT-3 mRNA levels and its receptor TrkC were elevated after 3 days, while NT-3 protein levels remained unaffected. The results demonstrate that voluntary exercise has a differential effect on NT-3 as well as its receptor TrkC in the neural and muscular components of the neuromuscular system, and emphasize the role of voluntary activity on the spinal cord and muscle.  相似文献   

3.
4.
Neurotrophins play a crucial role in the regulation of survival and the maintenance of specific functions for various populations of neurons. Neurotrophin-4 (NT-4) is most abundant in skeletal muscle, and is thought to promote sciatic nerve sprouting, inhibit agrin-induced acetylcholine receptor (AChR) clustering, evoke postsynaptic potentiation and induce mitochondrial proliferation. Using Western blot analysis, immunoprecipitation and immunohistochemistry, we investigated the distribution of NT-4 in slow- and fast-type muscles. We also tested the adaptive response of this protein in the mechanically overloaded muscle, in the regenerating muscle following bupivacaine injection and in the denervated muscle. Additionally, we investigated whether TrkB phosphorylation in the spinal cord and in the sciatic nerve occurs through the interaction with BDNF or NT-4 when the innervating muscle is damaged. Markedly more NT-4 was expressed in fast-type muscles compared with the slow types. TrkB protein was more frequently observed around the edge of myofibers (neuromuscular junction) of the soleus muscle compared with the gastrocnemius muscle. TrkB tyrosine phosphorylation occurred in the spinal cord but not in the sciatic nerve 24 h after bupivacaine injection of the innervating muscle. At the same time, the amount of TrkB co-precipitating with BDNF was markedly increased in the spinal cord. A rapid activation of TrkB (1-8 h) was also observed in the spinal cord after axotomy,while the amount of TrkB co-precipitating with NT-4 was markedly lower after axotomy. These results indicate that NT-4 is preferentially distributed in fast-type muscles. Furthermore, by interacting with BDNF and NT-4, the TrkB in the spinal cord may be important for the survival of motoneurons and outgrowth of injured peripheral axons following muscle damage.  相似文献   

5.
The changes in the expression of brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), and neurotrophin-4 (NT-4) in the rat neuromuscular system as a result of three different types of sciatic nerve injuries have been evaluated. The changes in mRNA and protein levels for BDNF, NT-3, and NT-4 in the soleus muscle and sciatic nerve were assessed 4-28 days after sciatic nerve transection (neurotmesis), sciatic nerve crush (axonotmesis), and mild acute compression (neurapraxia). BDNF mRNA levels increased dramatically with nerve transection in the soleus muscle and the sciatic nerve 7-14 days after injury, whereas the changes were low in other types of injury. The changes of protein levels for BDNF were also similar. The mRNA and the protein levels of NT-3 in the soleus muscle did not show any significant difference. The mRNA for NT-4 in the soleus muscle decreased from 4 to 14 days after sciatic nerve transection, and the protein level was also minimum 14 days after sciatic nerve transection. Our results indicate that the neurotrophic factors in the neuromuscular system could play a role in differentiating peripheral nerve injury.  相似文献   

6.
Neurotrophins play a crucial role in the regulation of survival and maintenance of specific functions of various populations of neurons. Brain-derived neurotrophic factor (BDNF), newrotrophin-3 (NT-3) and neurotrophin 4/5 (NT-4) have been shown to support motoneuron survival during embryonic development and, after birth, to protect motoneurons from degeneration after nerve lesion. We have compared the levels of these neurotrophins in skeletal muscle by quantitative Northern blot analysis, both during embryonic development and postnatally. We localized the sites of expression of these neurotrophins by in situ hybridisation and analysed the expression of trkB in the spinal cord by in situ hybridisation and immunohistochemistry. NT-3 is most abundantly expressed both during embryonic development and in the postnatal phase, followed by NT-4. The levels of BDNF are very low, in particular after birth. After nerve lesion, NT-3 mRNA essentially remained unchanged, whereas NT-4 mRNA rapidly decreased. The slow increase in BDNF expression seems to be essentially due to the expression in Schwann cells rather than skeletal muscle, demonstrated by in situ hybridisation. Our data indicate that motoneurons can receive trophic support from several members of the neurotrophin gene family during the period of naturally occurring cell death. Postnatally, the predominant ligand acting via trkB on motoneurons is NT-4, whereas BDNF expression seems to play a role mainly after nerve lesion. © 1995 Wiley-Liss, Inc.  相似文献   

7.
The aim of this study was to approach the question of neuronal dependence on neurotrophins during embryonic development in mice in a way other than gene targeting. We employed amyogenic mouse embryos and fetuses that develop without any skeletal myoblasts or skeletal muscle and consequently lose motor and proprioceptive neurons. We hypothesized that if, in spite of the complete inability to maintain motor and proprioceptive neurons, the remaining spinal and dorsal root ganglia tissues of amyogenic fetuses still contain any of the neurotrophins, that particular neurotrophin alone is not sufficient for the maintenance of motor and proprioceptive neurons. Moreover, if the remaining spinal and dorsal root ganglia tissues still contain any of the neurotrophins, that particular neurotrophin alone may be sufficient for the maintenance of the remaining neurons (i.e., mostly non-muscle- and a few muscle-innervating neurons). To test the role of the spinal cord and dorsal root ganglia tissues in the maintenance of its neurons, we performed immunohistochemistry employing double-mutant and control tissues and antibodies against neurotrophins and their receptors. Our data suggested that: (a) during the peak of motor neuron cell death, the spinal cord and dorsal root ganglia distribution of neurotrophins was not altered; (b) the distribution of BDNF, NT-4/5, TrkB and TrkC, and not NT-3, was necessary for the maintenance of the spinal cord motor neurons; (c) the distribution of BDNF, NT-4/5 and TrkC, and not NT-3 and Trk B, was necessary for the maintenance of the DRG proprioceptive neurons; (d) NT-3 was responsible for the maintenance of the remaining neurons and glia in the spinal cord and dorsal root ganglia (possibly via TrkB).  相似文献   

8.
Although numerous studies have examined the effects of neurotrophin treatment following spinal cord injury, few have examined the changes that occur in the neurotrophin receptors following either such damage or neurotrophin treatment. To determine what changes occur in neurotrophin receptor expression following spinal cord damage, adult rats received a midthoracic spinal cord hemisection alone or in combination with intrathecal application of brain-derived neurotrophic factor (BDNF) or neurotrophin-3 (NT-3). Using immunohistochemical and in situ hybridization techniques, p75, trkA, trkB, and trkC receptor expression was examined throughout the spinal cord. Results showed that trkA, full-length trkB, and trkC receptors were not present in the lesion site but had a normal expression pattern in uninjured parts of the spinal cord. In contrast, p75 receptor expression occurred on Schwann cells throughout the lesion site. BDNF and NT-3 (but not saline) applied to the lesion site increased this expression. In addition, the truncated trkB receptor was expressed in the border between the lesion and intact spinal cord. Truncated trkB receptor expression was also increased throughout the white matter ipsilateral to the lesion and BDNF (but not NT-3 or saline) prevented this increase. The study is the first to show changes in truncated trkB receptor expression that extend beyond the site of a spinal cord lesion and is one of the first to show that BDNF and NT-3 affect Schwann cells and/or p75 expression following spinal cord damage. These results indicate that changes in neurotrophin receptor expression following spinal cord injury could influence the availability of neurotrophins at the lesion site. In addition, neurotrophins may affect their own availability to damaged neurons by altering the expression of the p75 and truncated trkB receptor.  相似文献   

9.
Cycling exercise attenuates atrophy in hindlimb muscles and causes changes in spinal cord properties after spinal cord injury in rats. We hypothesized that exercising soleus muscle expresses genes that are potentially beneficial to the injured spinal cord. Rats underwent spinal cord injury at T10 and were exercised on a motor-driven bicycle. Soleus muscle and lumbar spinal cord tissue were used for messenger RNA (mRNA) analysis. Gene expression of brain-derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF) was elevated 11- and 14-fold, respectively, in soleus muscle after one bout of exercise performed 5 days after spinal cord transection. Also, c-fos and heat shock protein-27 (HSP27) mRNA abundance were increased 11- and 7-fold, respectively. When exercise was started 2 days after the injury, the changes in gene expression were not observed. By contrast, at 2 but not at 5 days after transection, expression of the HSP27 gene was elevated sixfold in the lumbar spinal cord, independent of exercise. Electromyographic activity in soleus muscles was also decreased at 2 days, indicating that the spinal cord was less permissive to exercise at this early time. Long-term exercise for 4 weeks attenuated muscle atrophy equally well in rats started at 2 days or 5 days after injury. We conclude that BDNF and GDNF released from exercising muscle may be involved in exercise-induced plasticity of the spinal cord. Furthermore, the data suggest that the lumbar spinal cord undergoes time-dependent changes that temporarily impede the ability of the muscle to respond to exercise.  相似文献   

10.
Li XL  Zhang W  Zhou X  Wang XY  Zhang HT  Qin DX  Zhang H  Li Q  Li M  Wang TH 《Neuropeptides》2007,41(3):135-143
Functional recovery of neurons in the spinal cord after physical injury is essentially abortive in clinical cases. As neurotrophins had been reported to be responsible, at least partially, for the lesion-induced recovery of spinal cord, it is not surprising that they have become the focus of numerous studies. Studies on endogenous neurotrophins, especially the three more important ones, nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) in injured spinal cord might provide some important clues in clinical treatment. Here we investigate the immunohistological expression of the above three factors at lower thoracic levels of the spinal cord as well as changes in the motor functions of the adult rat hindlimbs after cord transection. The injured rats were allowed to survive 3, 7, 14 and 21 days post operation (dpo). Flaccid paralysis was seen at 3 dpo following cord transection, however, hindlimb function showed partial recovery from 7 dpo to 21 dpo. The numbers of NGF, BDNF and NT-3 immunopositive neurons and their optical densities all increased in the lesion-induced cord. The immuno-expression of NGF and BDNF peaked at 7 dpo, while that of NT-3 peaked at 7 dpo and remained so at least up to 14 dpo. These results suggested that neurotrophins might play essential roles in functional recovery of after spinal cord injury, but the time points for the expression of the three factors differed somewhat.  相似文献   

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