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1.
The effect of colchicine on the transport of axonal protein in the chicken 总被引:8,自引:1,他引:7
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1. Small doses (1-10mug) of colchicine injected into the ventral horn of the spinal cord of the chicken caused paralysis in the legs. 2. Colchicine had no effect on the incorporation of leucine into proteins of the spinal cord but markedly decreased the total amount of protein flowing into the axons of the sciatic nerve. 3. This axonal flow of protein proceeded at two rates: a high rate (300mm/day) and a low rate (2mm/day). Although both groups of proteins were affected, the slow transport of protein was more profoundly blocked by colchicine. 4. The results suggest that axonal flow is dependent on the neurotubular system in the axon. 相似文献
2.
Axonal transport of enzymatically active botulinum toxin A (BTX-A) from periphery to the CNS has been described in facial and trigeminal nerve, leading to cleavage of synaptosomal-associated protein 25 (SNAP-25) in central nuclei. Aim of present study was to examine the existence of axonal transport of peripherally applied BTX-A to spinal cord via sciatic nerve. We employed BTX-A-cleaved SNAP-25 immunohistochemistry of lumbar spinal cord after intramuscular and subcutaneous hind limb injections, and intraneural BTX-A sciatic nerve injections. Truncated SNAP-25 in ipsilateral spinal cord ventral horns and dorsal horns appeared after single peripheral BTX-A administrations, even at low intramuscular dose applied (5 U/kg). Cleaved SNAP-25 appearance in the spinal cord after BTX-A injection into the sciatic nerve was prevented by proximal intrasciatic injection of colchicine (5 mM, 2 μl). Cleaved SNAP-25 in ventral horn, using choline-acetyltransferase (ChAT) double labeling, was localized within cholinergic neurons. These results extend the recent findings on BTX-A retrograde axonal transport in facial and trigeminal nerve. Appearance of truncated SNAP-25 in spinal cord following low-dose peripheral BTX-A suggest that the axonal transport of BTX-A occurs commonly following peripheral application. 相似文献
3.
Ccile Martinat Nadine Jarousse Marie-Christine Prvost Michel Brahic 《Journal of virology》1999,73(7):6093-6098
Following intracerebral inoculation, the DA strain of Theiler's virus sequentially infects neurons in the gray matter and glial cells in the white matter of the spinal cord. It persists in the latter throughout the life of the animal. Several observations suggest that the virus spreads from the gray to the white matter by axonal transport. In contrast, the neurovirulent GDVII strain causes a fatal encephalitis with lytic infection of neurons. It does not infect the white matter of the spinal cord efficiently and does not persist in survivors. The inability of this virus to infect the white matter could be due to a defect in axonal transport. Using footpad inoculations, we showed that the GDVII strain is, in fact, transported in axons. Transport was prevented by sectioning the sciatic nerve. The kinetics of transport and experiments using colchicine suggested that the virus uses microtubule-associated fast axonal transport. Our results show that a cardiovirus can spread by fast axonal transport and suggest that the inability of the GDVII strain to infect the white matter is not due to a defect in axonal transport. 相似文献
4.
A G Kobylianski? G Ia Bakalkin 《Zhurnal vysshe? nervno? deiatelnosti imeni I P Pavlova》1987,37(6):1131-1139
It has been found that bremazocine and met-enkephalin induce postural asymmetry in spinal rats under subarachnoidal and intravenous administration. Intravenous administration of bremazocine to intact animals--even if after it (an hour later) their spinal cord is sectioned--produces no asymmetry, i. e. the spinal cord section is necessary for asymmetry development. The magnitude of postural asymmetry and the side of limb flexion are not constant for each animal, but they change in time. Though, on the average, the percent of asymmetric animals and the ratio of left and right flexions in each group of animals are practically constant. When the spinal cord is sectioned at the T1-T4 level, the bremazocine and metenkephalin induce mainly the right-leg flexion: when the section is made at the T5-T9 level, the left-leg is bent, i. e. the flexion side depends on the level of the section. It is suggested that the ability of opioids to induce postural asymmetry is based on lateralization of opioid receptors in the rat spinal cord. 相似文献
5.
I P Shul'gina B I Klement'ev G A Vartanian 《Biulleten' eksperimental'no? biologii i meditsiny》1984,98(10):394-396
The role of the pituitary in the mechanisms of posttraumatic reorganizations of the segmental apparatus was studied. Hypophysectomized rats failed to demonstrate postural asymmetry after spinal cord hemisection. The lack of asymmetry is connected with a considerable decrease in postural asymmetry factor activity in the cerebrospinal fluid and cerebral tissue. It was established that pituitary tissue is characterized by the maximal level of postural asymmetry factor activity after hemisection. 相似文献
6.
E I Varlinskaia M G Rogachi? B I Klement'ev G A Vartanian 《Biulleten' eksperimental'no? biologii i meditsiny》1984,98(9):281-283
The authors studied the time-course of functional rearrangements of the segmental apparatus after unilateral injury of the rat motor cortex. It was found that one day after injury the postural asymmetry of the hind limbs was fixed by the lumbal region of the spinal cord. This functional state of the segmental apparatus lasted 10 days after injury in the presence of the maximal activity of postural asymmetry factor (PAF) in the CSF and increasing activity of the factor in the brain tissue. Recovery of the segmental apparatus to symmetrical function by the end of the third week following injury was accompanied by PAF inactivation. 相似文献
7.
Axonal transport blockade and denervation have qualitatively different effects upon skeletal muscle metabolism 总被引:1,自引:0,他引:1
B U Ramírez 《Journal of neurobiology》1984,15(2):119-126
The activity and isoenzyme pattern of muscle lactic dehydrogenase (LDH) was measured at different times after axonal transport blockade by colchicine or after denervation. After denervation, total LDH activity decreased and the isoenzyme pattern was altered, LDH-1 being the most affected form. In contrast, after axonal transport blockade there was a decrease in LDH activity but the isoenzyme pattern was not modified. Denervation abolishes both nerve-evoked muscle activity and the release of neuro trophic substances from the nerve whereas colchicine blocks axonal transport without affecting the nerve capacity to conduct action potentials or neuromuscular transmission. It is then concluded that nerve-evoked muscle activity is the most important factor in the regulation of muscle LDH isoenzyme distribution. On the other hand, muscle metabolism can also be regulated by axonally transported molecules. The results presented here show that there is a qualitative difference between the effects of denervation and those of axonal transport blockade upon the muscle, since only denervation altered the isoenzyme pattern of muscle LDH. 相似文献
8.
To determine whether axonal transport plays a role in the establishment of long-lasting changes in synaptic transmission, the effects of colchicine on transport and on synaptic modifications induced by hyperactivity were studied in the nerve cord of the cockroach Blatta orientalis. Application of a lead weight on the insect's dorsum, and the consequent exaggerated use of antigravity reflexes, facilitated synaptic transmission along a particular nervous pathway in the metathoracic ganglion. Application of colchicine in the prothoracic ganglion reversibly blocked such synaptic facilitation and temporarily interfered with the transport of proteins along the cord. Five components of axonal transport, moving at 2, 10, 25, 75, and 150 mm/day, were altered by colchicine treatment with a temporal course that coincided with the reversible inhibition of synaptic facilitation. These results were brought about by colchicine acting directly on axonal transport at the level of the prothoracic ganglion, rather than on synaptic transmission measured at the metathoracic ganglion. The temporal correlation observed between the effects of colchicine on axonal transport and on synaptic facilitation strongly suggest that the transport process is essential for long-lasting synaptic modifications to take place. 相似文献
9.
—The half-life of tryptophan 5-hydroxylase (EC 1.14.3) in rats was estimated from the return of enzyme activity after administration of p-chlorophenylalanine and from the decline of enzyme activity in spinal cord after transection or an intraspinal injection of colchicine. The half-life was 2–3 days. Axonal transport of enzyme, estimated from the reappearance of activity in consecutive portions of spinal cord after treatment with p-chlorophenylalanine, was of the order of 5–7 mm/day. This rate is characteristic of 'slow’axonal flow. Our results suggest that changes in the synthesis of new enzyme are probably not responsible for acute changes in the turnover of serotonin. 相似文献
10.
FGF22 signaling regulates synapse formation during post‐injury remodeling of the spinal cord
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Anne Jacobi Kristina Loy Anja M Schmalz Mikael Hellsten Hisashi Umemori Martin Kerschensteiner Florence M Bareyre 《The EMBO journal》2015,34(9):1231-1243
The remodeling of axonal circuits after injury requires the formation of new synaptic contacts to enable functional recovery. Which molecular signals initiate such axonal and synaptic reorganisation in the adult central nervous system is currently unknown. Here, we identify FGF22 as a key regulator of circuit remodeling in the injured spinal cord. We show that FGF22 is produced by spinal relay neurons, while its main receptors FGFR1 and FGFR2 are expressed by cortical projection neurons. FGF22 deficiency or the targeted deletion of FGFR1 and FGFR2 in the hindlimb motor cortex limits the formation of new synapses between corticospinal collaterals and relay neurons, delays their molecular maturation, and impedes functional recovery in a mouse model of spinal cord injury. These results establish FGF22 as a synaptogenic mediator in the adult nervous system and a crucial regulator of synapse formation and maturation during post‐injury remodeling in the spinal cord. 相似文献
11.
G A Vartanian S V Shatik A V Tokarev B I Klement'ev 《Biulleten' eksperimental'no? biologii i meditsiny》1989,107(4):404-407
The distribution of the low-molecular weight and high-molecular weight postural asymmetry factors (FPA) activity in the left and right parts of the lumbal region of the rat spinal cord was studied. Low-molecular weight FPA induces flexion of the hind limb ipsilateral to the half of the spinal cord from which FPA was isolated, while high-molecular weight FPA induces contralateral flexion. The activities of the low- and high-molecular weight FPAs in each half of the spinal cord are comparable in normal rat. After the suction lesion of the motor areas in the left hemisphere the increase of the low-molecular weight FPA activity in the right half of the lumbal region of the spinal cord was observed. 相似文献
12.
Met- and Leu-enkephalin applied subarachnoidally into the rostral portion of a transected spinal cord (at the T6-T7 level) induce postural asymmetry of the hind limbs in rats, Met-enkephalin being predominantly responsible for the flexion of the right, and Leu-enkephalin of the left, hind leg. The blood serum of rats injected with Met-enkephalin contains a factor which, when administered subarachnoidally into the caudal portion of the transected spinal cord, is capable of inducing the hind limb postural asymmetry--predominantly, with the right leg flexion. This factor is inactivated by papain and differs from Met- and Leu-enkephalin in chromatographic properties. Apparently, Met-enkephalin induces the release of a peptide factor into the blood, from the brain or organs innervated by the neurons lying above the cut. It is then carried with the blood to the hind limbs and effects the hind limb postural asymmetry. 相似文献
13.
Changes in the amounts of cytoskeletal proteins within the perikarya and axons of regenerating frog motoneurons 总被引:2,自引:2,他引:0
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Changes in the amounts of tubulin, actin, and neurofilament polypeptides were found in regenerating motoneurons of grass frogs during the period of axonal elongation. Ventral roots 9 and 10 were transected unilaterally about 7 mm from the spinal cord. 35 d later, [3H]colchicine binding had decreased in the proximal stumps to approximately one-half of contralateral control values, well before the regenerating motor axons had reinnervated skeletal muscles of the hind limb. [3H]colchicine binding did not change significantly in the operated halves of the 9th and 10th spinal cord segments over a 75-d period. The relative amounts of actin, tubulin, and neurofilament polypeptides in the operated ventral roots were measured by quantitative densitometry of stained two-dimensional electrophoretic gels. Alpha-tubulin, beta-tubulin, and the 68,000 molecular weight subunit of neurofilaments (NF68) decreased within the transected ventral roots to 78%, 57%, and less than 15% of control values, respectively. The amount of actin increased to 132% of control values within the operated ventral roots, although this change was not statistically significant. Opposite changes were found within motoneuronal cell bodies isolated from the spinal cord. The relative amounts of alpha-tubulin, beta-tubulin and NF68 within axotomized perikarya increased, respectively, to 191%, 146%, and 144% of that in control perikarya isolated from the contralateral side of the spinal cord. Thus, the changes in NF68 and tubulin did not occur uniformly throughout the injured cells. The possible structural and functional consequences of these changes are discussed. 相似文献
14.
A G Kobylianski? G Ia Bakalkin 《Zhurnal vysshe? nervno? deiatelnosti imeni I P Pavlova》1988,38(1):122-128
Opioid kappa-agonists bremazocine and dynorphin (1-13), sigma-agonist SKF 10.047 and delta-agonist D-Ala2, D-Leu5-enkephalin (DADL) induce postural asymmetry of rats hind limbs under subarachnoidal administration below the level of spinal cord section (T3-T4). The side of the flexed leg depends on the opioid agonist type: bremazocine and dynorphin (1-13) induce predominantly right flexion. SKF 10.047--the left flexion, but not in all doses, DADL--in small doses (1 and 100 pg per animal)--of the right one, in larger doses (up to 10 ng per animal)--of the left one. Saline and opiate mu-agonist morphine do not induce postural asymmetry. Opiate antagonist naloxone prevents asymmetry development when injected prior opioid agonists, and also decreases the number of asymmetries induced by these agonists. Naloxone alone does not influence the per cent of animals with pose asymmetry. The opioid receptors are involved in asymmetry development. The revealed ability of opioid kappa-, delta- and sigma-agonists may be based on lateralization of opioid receptors in the rat spinal cord. 相似文献
15.
Starlyn L. M. Okada Nicole S. Stivers Peter K. Stys David P. Stirling 《Journal of visualized experiments : JoVE》2014,(93)
Injured CNS axons fail to regenerate and often retract away from the injury site. Axons spared from the initial injury may later undergo secondary axonal degeneration. Lack of growth cone formation, regeneration, and loss of additional myelinated axonal projections within the spinal cord greatly limits neurological recovery following injury. To assess how central myelinated axons of the spinal cord respond to injury, we developed an ex vivo living spinal cord model utilizing transgenic mice that express yellow fluorescent protein in axons and a focal and highly reproducible laser-induced spinal cord injury to document the fate of axons and myelin (lipophilic fluorescent dye Nile Red) over time using two-photon excitation time-lapse microscopy. Dynamic processes such as acute axonal injury, axonal retraction, and myelin degeneration are best studied in real-time. However, the non-focal nature of contusion-based injuries and movement artifacts encountered during in vivo spinal cord imaging make differentiating primary and secondary axonal injury responses using high resolution microscopy challenging. The ex vivo spinal cord model described here mimics several aspects of clinically relevant contusion/compression-induced axonal pathologies including axonal swelling, spheroid formation, axonal transection, and peri-axonal swelling providing a useful model to study these dynamic processes in real-time. Major advantages of this model are excellent spatiotemporal resolution that allows differentiation between the primary insult that directly injures axons and secondary injury mechanisms; controlled infusion of reagents directly to the perfusate bathing the cord; precise alterations of the environmental milieu (e.g., calcium, sodium ions, known contributors to axonal injury, but near impossible to manipulate in vivo); and murine models also offer an advantage as they provide an opportunity to visualize and manipulate genetically identified cell populations and subcellular structures. Here, we describe how to isolate and image the living spinal cord from mice to capture dynamics of acute axonal injury. 相似文献
16.
FAST AXONAL TRANSPORT IN VITRO IN THE SCIATIC SYSTEM OF THE FROG 总被引:7,自引:3,他引:4
Abstract— An in vitro system from the frog has been used to study fast axonal protein transport. The preparation, which was incubated in a specially made chamber, consisted of the gastrocnemius muscle, the sciatic nerve, the dorsal ganglia and part of the spinal cord. The parts were separated from each other by silicone grease barriers, which made it possible to follow the migration of labelled proteins from the spinal cord and ganglia, along the sciatic nerve, towards the muscle. About 80 per cent of transported proteins in the sciatic nerve originated from the dorsal spinal ganglia and moved antidromically at a rate of 60–90 mm per day at 18°C. The rapidly transported proteins were 90 per cent particulate and mainly associated with structures sedimenting in the microsomal fraction.
The effects of cyclohexirnide showed that the synthesis of rapidly moving proteins and their transport were separate processes. A low concentration of colchicine inhibited the transport when it was present in the medium surrounding the ganglia, but had no effect even at a higher concentration, when it was added to the nerve compartment. The presence of vinblastine at a low concentration in either of the two compartments completely arrested the protein transport. Likewise N-ethylmaleimide or p-chloromercuribenzene sulphonic acid in the nerve medium effectively blocked the fast transport. Results from experiments performed to test the possibility of disto-proximal flow and of transfer of proteins from the muscle to the nerve are discussed. 相似文献
The effects of cyclohexirnide showed that the synthesis of rapidly moving proteins and their transport were separate processes. A low concentration of colchicine inhibited the transport when it was present in the medium surrounding the ganglia, but had no effect even at a higher concentration, when it was added to the nerve compartment. The presence of vinblastine at a low concentration in either of the two compartments completely arrested the protein transport. Likewise N-ethylmaleimide or p-chloromercuribenzene sulphonic acid in the nerve medium effectively blocked the fast transport. Results from experiments performed to test the possibility of disto-proximal flow and of transfer of proteins from the muscle to the nerve are discussed. 相似文献
17.
Abstract: Calcium is required to sustain fast axonal transport in sensory neurons of frog and cat. We studied the Ca2+ dependence of fast axonal transport in the motoneurons of the lower spinal cord from frog. The accumulation of acetylcholinesterase at a crush on the ventral roots was used to follow axonal transport. Two types of experiments were performed: modification of the medium bathing the ventral roots, alone, and modification of the medium bathing the spinal cord and ventral roots. Incubation (17-18 h) of the ventral roots in Ca2+ -free medium markedly inhibited acetylcholinesterase transport, a finding that demonstrates a Ca2+ requirement for fast axonal transport in motoneurons; when 4 m M MgCl2 was added to the Ca2+ -free medium, transport was also greatly reduced. During incubation of the ventral roots in normal medium supplemented with 0.18 m M CoCl2 transport proceeded normally; but when the Co2+ concentration was raised to 1.8 m M , transport was diminished as drastically as in the Ca2+ -free medium. Incubation of the spinal cord and ventral roots in medium containing 0.18 m M CoCl2 did not reduce the accumulation of acetylcholinesterase at the crush. Similarly, accumulation of acetylcholinesterase at a crush on the dorsal root was not significantly reduced by exposure of the dorsal root ganglion and root to 0.18 m M Co2+ . Exposure of sensory cell bodies to 0.18 m M Co2+ thus produces differential effects on transport of acetylcholinesterase and on transport of newly synthesized radiolabeled protein. 相似文献
18.
Goldshmit Y Spanevello MD Tajouri S Li L Rogers F Pearse M Galea M Bartlett PF Boyd AW Turnley AM 《PloS one》2011,6(9):e24636
Upregulation and activation of developmental axon guidance molecules, such as semaphorins and members of the Eph receptor tyrosine kinase family and their ligands, the ephrins, play a role in the inhibition of axonal regeneration following injury to the central nervous system. Previously we have demonstrated in a knockout model that axonal regeneration following spinal cord injury is promoted in the absence of the axon guidance protein EphA4. Antagonism of EphA4 was therefore proposed as a potential therapy to promote recovery from spinal cord injury. To further assess this potential, two soluble recombinant blockers of EphA4, unclustered ephrin-A5-Fc and EphA4-Fc, were examined for their ability to promote axonal regeneration and to improve functional outcome following spinal cord hemisection in wildtype mice. A 2-week administration of either of these blockers following spinal cord injury was sufficient to promote substantial axonal regeneration and functional recovery by 5 weeks following injury. Both inhibitors produced a moderate reduction in astrocytic gliosis, indicating that much of the effect of the blockers may be due to promotion of axon growth. These studies provide definitive evidence that soluble inhibitors of EphA4 function offer considerable therapeutic potential for the treatment of spinal cord injury and may have broader potential for the treatment of other central nervous system injuries. 相似文献
19.
K Suzuki 《Archives italiennes de biologie》1985,123(3):155-170
Cells of origin of the spinal projections from the brainstem of the cat have been studied by means of retrograde axonal transport of horseradish peroxidase (HRP). Following injections of HRP into various levels of the spinal cord, many labeled cells were found in several structures in the brainstem. The labeled cells occurred in the raphe nuclei, reticular formation, vestibular complex, and nuclei of the dorsolateral pontine tegmentum. In the dorsolateral pontine tegmentum, many labeled cells were found in the nuclei of locus coeruleus, subcoeruleus and K?lliker-Fuse. In the coeruleus and subcoeruleus, the greatest number of labeled cells were found, when HRP was injected into the sacral cord. No difference emerged, however, in the number of labeled cells appearing in the K?lliker-Fuse nucleus after injection of the enzyme into different levels of the spinal cord. It appears that neurons in the lateral vestibular nucleus which project to different levels of the spinal cord are located in different parts of this nucleus. 相似文献