scholarly journals Localized Induction of Wild-Type and Mutant Alpha-Synuclein Aggregation Reveals Propagation along Neuroanatomical Tracts

2018 ◽  
Vol 92 (18) ◽  
Author(s):  
Jacob I. Ayers ◽  
Cara J. Riffe ◽  
Zachary A. Sorrentino ◽  
Jeffrey Diamond ◽  
Eric Fagerli ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Sciatic Nerve ◽  
Prion Protein ◽  
Motor Neurons ◽  
Brain Regions ◽  
Alpha Synuclein ◽  
Lumbar Spinal Cord ◽  
The Central Nervous System ◽  
Lumbar Spinal ◽  
Alpha Synuclein Aggregation

ABSTRACTMisfolded alpha-synuclein (αS) may exhibit a number of characteristics similar to those of the prion protein, including the apparent ability to spread along neuroanatomical connections. The demonstration for this mechanism of spread is largely based on the intracerebral injections of preaggregated αS seeds in mice, in which it cannot be excluded that diffuse, surgical perturbations and hematogenous spread also contribute to the propagation of pathology. For this reason, we have utilized the sciatic nerve as a route of injection to force the inoculum into the lumbar spinal cord and induce a localized site for the onset of αS inclusion pathology. Our results demonstrate that mouse αS fibrils (fibs) injected unilaterally in the sciatic nerve are efficient in inducing pathology and the onset of paralytic symptoms in both the M83 and M20 lines of αS transgenic mice. In addition, a spatiotemporal study of these injections revealed a predictable spread of pathology to brain regions whose axons synapse directly on ventral motor neurons in the spinal cord, strongly supporting axonal transport as a mechanism of spread of the αS inducing, or seeding, factor. We also revealed a relatively decreased efficiency for human αS fibs containing the E46K mutation to induce disease via this injection paradigm, supportive of recent studies demonstrating a diminished ability of this mutant αS to undergo aggregate induction. These results further demonstrate prion-like properties for αS by the ability for a progression and spread of αS inclusion pathology along neuroanatomical connections.IMPORTANCEThe accumulation of alpha-synuclein (αS) inclusions is a hallmark feature of Parkinson's disease (PD) and PD-related diseases. Recently, a number of studies have demonstrated similarities between the prion protein and αS, including its ability to spread along neuroanatomical tracts throughout the central nervous system (CNS). However, there are caveats in each of these studies in which the injection routes used had the potential to result in a widespread dissemination of the αS-containing inocula, making it difficult to precisely define the mechanisms of spread. In this study, we assessed the spread of pathology following a localized induction of αS inclusions in the lumbar spinal cord following a unilateral injection in the sciatic nerve. Using this paradigm, we demonstrated the ability for αS inclusion spread and/or induction along neuroanatomical tracts within the CNS of two αS-overexpressing mouse models.

scholarly journals Co-injection of wheat germ agglutinin-HRP and choleragenoid-HRP into the sciatic nerve of the rat blocks transganglionic transport.

1995 ◽  
Vol 43 (5) ◽  
pp. 489-495 ◽  
Author(s):  
H Liu ◽  
I J Llewellyn-Smith ◽  
A I Basbaum
Keyword(s):  
Spinal Cord ◽  
Sciatic Nerve ◽  
Motor Neurons ◽  
Wheat Germ Agglutinin ◽  
Wheat Germ ◽  
Lumbar Spinal Cord ◽  
Retrograde Labeling ◽  
Afferent Fibers ◽  
Primary Afferent Fibers ◽  
Lumbar Spinal

We report on the surprising loss of transganglionic and retrograde labeling in the spinal cord of the rat after co-injection of the tracers wheat germ agglutinin-HRP (WGA-HRP) and choleragenoid toxin-HRP (CTB-HRP) into the sciatic nerve. Injection of WGA-HRP alone produced a pattern of transganglionic label consistent with transport by small-diameter primary afferent fibers. Small cell bodies were labeled in the ipsilateral dorsal root ganglion (DRG) and there was dense terminal labeling in the superficial dorsal horn of the lumbar spinal cord. Injection of CTB-HRP alone produced a pattern of transganglionic labeling consistent with transport by large-diameter primary afferent fibers. Large cell bodies were labeled in the DRG and there was dense terminal labeling in the nucleus proprius (Laminae III-V) in the spinal cord. CTB-HRP also produced extensive retrograde labeling of ventral horn motor neurons. When the two tracers were co-injected, we found few labeled cells in the ipsilateral DRG and there was almost complete loss of transganglionic terminal labeling in the lumbar spinal cord. Retrograde labeling of motor neurons was also significantly reduced. Even when one of the tracers (e.g., WGA-HRP) was injected 24 hr after and up to 10 mm proximal to the site of the first tracer (e.g., CTB-HRP), an inhibitory interaction was detected. The labeling pattern was always characteristic of the first tracer injected.(ABSTRACT TRUNCATED AT 250 WORDS)

Does Motor Learning Occur in the Spinal Cord?

1997 ◽  
Vol 3 (5) ◽  
pp. 287-294 ◽  
Author(s):  
V. Reggie Edgerton ◽  
Roland R. Roy ◽  
Ray De Leon Niranjala Tillakaratne ◽  
John A. Hodgson
Keyword(s):  
Spinal Cord ◽  
Motor Task ◽  
Lumbar Spinal Cord ◽  
Lumbosacral Spinal Cord ◽  
Patterns Of Use ◽  
The Neural Network ◽  
The Central Nervous System ◽  
Network Plasticity ◽  
Lumbar Spinal ◽  
The Brain

It is becoming clear that the plasticity of the sensory-motor networks of the adult mammalian lumbosacral spinal cord is much greater than and is more dependent on the specific patterns of use than has been previously assumed. Using a wide variety of experimental paradigms in which the lumbar spinal cord is isolated from the brain, it has been shown that the lumbosacral spinal cord can learn to execute stepping or standing more successfully if that specific task is practiced. It also appears that the sensory input associated with the motor task and/or the manner in which it is interpreted by the spinal cord are important components of the neural network plasticity. Early evidence suggests that several neurotransmitter systems in the spinal cord, to include glycinergic and GABAergic systems, adapt to repetitive use. These studies extend a growing body of evidence suggesting that memory and learning are widely distributed phenomena within the central nervous system. NEUROSCIENTIST 3:287–294, 1997

scholarly journals Locomotor Training Increases Synaptic Structure With High NGL-2 Expression After Spinal Cord Hemisection

2019 ◽  
Vol 33 (3) ◽  
pp. 225-231 ◽  
Author(s):  
Kazu Kobayakawa ◽  
Kyleigh Alexis DePetro ◽  
Hui Zhong ◽  
Bau Pham ◽  
Masamitsu Hara ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Motor Neurons ◽  
Ventral Horn ◽  
Lumbar Spinal Cord ◽  
Locomotor Training ◽  
Synaptic Structure ◽  
Cord Injury ◽  
Lumbar Spinal ◽  
Spinal Cord Hemisection ◽  
Activity Dependent

Background. We previously demonstrated that step training leads to reorganization of neuronal networks in the lumbar spinal cord of rodents after a hemisection (HX) injury and step training, including increases excitability of spinally evoked potentials in hindlimb motor neurons. Methods. In this study, we investigated changes in RNA expression and synapse number using RNA-Seq and immunohistochemistry of the lumbar spinal cord 23 days after a mid-thoracic HX in rats with and without post-HX step training. Results. Gene Ontology (GO) term clustering demonstrated that expression levels of 36 synapse-related genes were increased in trained compared with nontrained rats. Many synaptic genes were upregulated in trained rats, but Lrrc4 (coding NGL-2) was the most highly expressed in the lumbar spinal cord caudal to the HX lesion. Trained rats also had a higher number of NGL-2/synaptophysin synaptic puncta in the lumbar ventral horn. Conclusions. Our findings demonstrate clear activity-dependent regulation of synapse-related gene expression post-HX. This effect is consistent with the concept that activity-dependent phenomena can provide a mechanistic drive for epigenetic neuronal group selection in the shaping of the reorganization of synaptic networks to learn the locomotion task being trained after spinal cord injury.

scholarly journals Tail Nerve Electrical Stimulation and Electro-Acupuncture Can Protect Spinal Motor Neurons and Alleviate Muscle Atrophy after Spinal Cord Transection in Rats

2017 ◽  
Vol 2017 ◽  
pp. 1-11 ◽  
Author(s):  
Yu-Ting Zhang ◽  
Hui Jin ◽  
Jun-Hua Wang ◽  
Lan-Yu Wen ◽  
Yang Yang ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Electrical Stimulation ◽  
Muscle Atrophy ◽  
Motor Neurons ◽  
Lumbar Spinal Cord ◽  
Hindlimb Muscle ◽  
Neurotrophin 3 ◽  
Spinal Cord Segment ◽  
Cord Injury ◽  
Lumbar Spinal

Spinal cord injury (SCI) often results in death of spinal neurons and atrophy of muscles which they govern. Thus, following SCI, reorganizing the lumbar spinal sensorimotor pathways is crucial to alleviate muscle atrophy. Tail nerve electrical stimulation (TANES) has been shown to activate the central pattern generator (CPG) and improve the locomotion recovery of spinal contused rats. Electroacupuncture (EA) is a traditional Chinese medical practice which has been proven to have a neural protective effect. Here, we examined the effects of TANES and EA on lumbar motor neurons and hindlimb muscle in spinal transected rats, respectively. From the third day postsurgery, rats in the TANES group were treated 5 times a week and those in the EA group were treated once every other day. Four weeks later, both TANES and EA showed a significant impact in promoting survival of lumbar motor neurons and expression of choline acetyltransferase (ChAT) and ameliorating atrophy of hindlimb muscle after SCI. Meanwhile, the expression of neurotrophin-3 (NT-3) in the same spinal cord segment was significantly increased. These findings suggest that TANES and EA can augment the expression of NT-3 in the lumbar spinal cord that appears to protect the motor neurons as well as alleviate muscle atrophy.

mRNA and protein expression and activities of nitric oxide synthases in the lumbar spinal cord of neonatal rats after sciatic nerve transection and melatonin administration

2006 ◽  
Vol 407 (2) ◽  
pp. 182-187 ◽  
Author(s):  
Fábio Rogério ◽  
Simone Aparecida Teixeira ◽  
Hamilton Jordão Júnior ◽  
Carla Cristina Judice Maria ◽  
André Schwambach Vieira ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Spinal Cord ◽  
Sciatic Nerve ◽  
Lumbar Spinal Cord ◽  
Nerve Transection ◽  
Neonatal Rats ◽  
Sciatic Nerve Transection ◽  
Melatonin Administration ◽  
Mrna And Protein Expression ◽  
Lumbar Spinal

scholarly journals Slc6a4, Tph2, Htr1b, Htr2a genes expression in the mouse spinal cord after microgravity exposure simulation on earth

2020 ◽  
Vol 101 (5) ◽  
pp. 698-703
Author(s):  
M S Kuznetsov ◽  
A N Lisyukov ◽  
M A Davleeva ◽  
A A Izmailov
Keyword(s):  
Spinal Cord ◽  
Hindlimb Unloading ◽  
Synaptic Proteins ◽  
Expression Level ◽  
Lumbar Spinal Cord ◽  
Control Group ◽  
Genes Encoding ◽  
The Central Nervous System ◽  
Recovery Group ◽  
Lumbar Spinal

Aim. To determine the level of gene expression of the serotonergic neurotransmission system (Slc6a4, Tph2, Htr1b, Htr2a) in the cervical and lumbar enlargement of the spinal cord for mice after 30-day microgravity exposure simulation by using the antiorthostatic unloading model by Morey-Holton et al. and a subsequent 7-dayrecovery period. Methods. The experimental animals were divided into three groups: Unloading group with mice undergoes hindlimb-unloading procedure for 30 days (n=5); Recovery group with mice undergoes hindlimb-unloading procedure for 30 days, followed by readaptation within 7 days (n=5); Control group with mice kept at standard vivarium conditions (n=5). The expression level of genes encoding synaptic proteins in the central nervous system was estimated by a real-time polymerase chain reaction. Results. There were no statistically significant differences between the studied groups regarding the Tph2, Htr1b, and Htr2a expressions in the cervical and lumbar enlargement of the spinal cord. Compared to the Control group, a statistically significant increase (6.3 times) in the level of Slc6a4 expression in the lumbar spinal cord was revealed after microgravity exposure simulation (Unloading group), followed by a 3-fold decrease during the readaptation period (Recovery group ). Conclusion. The expression level of the Slc6a4 gene, which encodes carrier protein involved in the function of serotonergic synapses, may indicate the potential involvement of this neurotransmitter system in the pathogenesis of movement disorders after microgravity exposure simulation on earth.

scholarly journals Nimodipine Promotes Functional Recovery After Spinal Cord Injury in Rats

2021 ◽  
Vol 12 ◽  
Author(s):  
Fangliang Guo ◽  
Xiaolong Zheng ◽  
Ziyu He ◽  
Ruoying Zhang ◽  
Song Zhang ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Motor Neurons ◽  
Hind Limb ◽  
Term Treatment ◽  
Bladder Function ◽  
Lumbar Spinal Cord ◽  
Long Term Treatment ◽  
Cord Injury ◽  
Lumbar Spinal

Spinal cord injury (SCI) is a devastating condition that results in severe motor, sensory, and autonomic dysfunction. The L-/T-type calcium channel blocker nimodipine (NMD) exerts a protective effect on neuronal injury; however, the protective effects of long-term administration of NMD in subjects with SCI remain unknown. Thus, the aim of this study was to evaluate the role of long-term treatment with NMD on a clinically relevant SCI model. Female rats with SCI induced by 25 mm contusion were subcutaneously injected with vehicle or 10 mg/kg NMD daily for six consecutive weeks. We monitored the motor score, hind limb grip strength, pain-related behaviors, and bladder function in this study to assess the efficacy of NMD in rats with SCI. Rats treated with NMD showed improvements in locomotion, pain-related behaviors, and spasticity-like symptoms, but not in open-field spontaneous activity, hind limb grip strength or bladder function. SCI lesion areas and perilesional neuronal numbers, gliosis and calcitonin gene-related peptide (CGRP+) fiber sprouting in the lumbar spinal cord and the expression of K+–Cl− cotransporter 2 (KCC2) on lumbar motor neurons were also observed to further explore the possible protective mechanisms of NMD. NMD-treated rats showed greater tissue preservation with reduced lesion areas and increased perilesional neuronal sparing. NMD-treated rats also showed improvements in gliosis, CGRP+ fiber sprouting in the lumbar spinal cord, and KCC2 expression in lumbar motor neurons. Together, these results indicate that long-term treatment with NMD improves functional recovery after SCI, which may provide a potential therapeutic strategy for the treatment of SCI.

scholarly journals Effects of chronic spinal cord injury on relationships among ion channel and receptor mRNAs in mouse lumbar spinal cord

2018 ◽  
Author(s):  
Virginia B. Garcia ◽  
Matthew D. Abbinanti ◽  
Ronald M. Harris-Warrick ◽  
David J. Schulz
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Ion Channel ◽  
Motor Neurons ◽  
Receptor Expression ◽  
Lumbar Spinal Cord ◽  
Mrna Levels ◽  
Absolute Quantitation ◽  
Cord Injury ◽  
Lumbar Spinal

ABSTRACTSpinal cord injury (SCI) causes widespread changes in gene expression of the spinal cord, even in the undamaged spinal cord below the level of the lesion. Less is known about changes in the correlated expression of genes after SCI. We investigated gene co-expression networks among voltage-gated ion channel and neurotransmitter receptor mRNA levels using quantitative RT-PCR in longitudinal slices of the mouse lumbar spinal cord in control and chronic SCI animals. These longitudinal slices were made from the ventral surface of the cord, thus forming slices relatively enriched in motor neurons or interneurons. We performed absolute quantitation of mRNA copy number for 50 ion channel or receptor transcripts from each sample, and used multiple correlation analyses to detect patterns in correlated mRNA levels across all pairs of genes. The majority of channels and receptors changed in expression as a result of chronic SCI, but did so differently across slice levels. Furthermore, motor neuron enriched slices experienced an overall loss of correlated channel and receptor expression, while interneuron slices showed a dramatic increase in the number of positively correlated transcripts. These correlation profiles suggest that spinal cord injury induces distinct changes across cell types in the organization of gene co-expression networks for ion channels and transmitter receptors.

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