scholarly journals Age-Dependent Aggregation of α-Synuclein in the Nervous System of Gut-Brain Axis is Associated with Caspase-1 Activation

2021 ◽  
Author(s):  
Qi Hu ◽  
Mei Hong ◽  
Mengyang Huang ◽  
Quan Gong ◽  
Xiaofan Zhang ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Nervous System ◽  
Dopamine Synthesis ◽  
Thoracic Spinal Cord ◽  
Caspase 1 ◽  
Thoracic Spinal ◽  
Age Dependent ◽  
Rate Limiting ◽  
Old Mice

Abstract α-Synuclein (α-Syn) plays a key role in the development of Parkinson’ desease (PD). As aging is acknowledged to be the greatest risk factor for PD, here we investigated α-Syn expression in the ileum, thoracic spinal cord, and midbrain of young (1-month-old), middle-aged (6-, 12-month-old) to old (18-month-old) mice. We demonstrated that both the levels of α-Syn monomers, oligomers and ratios of oligomers to monomers were increased with aging in the ileum, thoracic spinal cord, and midbrain. Whereas, the expression of tyrosine hydroxylase (TH), the rate-limiting enzyme for dopamine synthesis, was decreased with aging in the midbrain. We failed to find corresponding α-Syn mRNA increase with aging. However, we found an increased expression of caspase-1 in the ileum, thoracic spinal cord, and midbrain. A specific caspase-1 inhibitor VX765 significantly reduced levels of both the α-Syn monomers and oligomers triggered by the rotenone in vitro. Taken together, the increase in α-Syn aggregation with aging might not occur first in the gut, but simultaneously in the nervous system of gut-brain axis.. The mechanism of the age-dependent aggregation of α-Syn in nervous system is likely triggered by the aging-related caspase-1 activation.

scholarly journals Remodeling of lumbar motor circuitry remote to a thoracic spinal cord injury promotes locomotor recovery

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Ying Wang ◽  
Wei Wu ◽  
Xiangbing Wu ◽  
Yan Sun ◽  
Yi P Zhang ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Targeted Delivery ◽  
Neural Circuit ◽  
Thoracic Spinal Cord ◽  
Spinal Cord Neurons ◽  
Thoracic Spinal ◽  
Virus Serotype ◽  
Cord Injury

Retrogradely-transported neurotrophin signaling plays an important role in regulating neural circuit specificity. Here we investigated whether targeted delivery of neurotrophin-3 (NT-3) to lumbar motoneurons (MNs) caudal to a thoracic (T10) contusive spinal cord injury (SCI) could modulate dendritic patterning and synapse formation of the lumbar MNs. In vitro, Adeno-associated virus serotype two overexpressing NT-3 (AAV-NT-3) induced NT-3 expression and neurite outgrowth in cultured spinal cord neurons. In vivo, targeted delivery of AAV-NT-3 into transiently demyelinated adult mouse sciatic nerves led to the retrograde transportation of NT-3 to the lumbar MNs, significantly attenuating SCI-induced lumbar MN dendritic atrophy. NT-3 enhanced sprouting and synaptic formation of descending serotonergic, dopaminergic, and propriospinal axons on lumbar MNs, parallel to improved behavioral recovery. Thus, retrogradely transported NT-3 stimulated remodeling of lumbar neural circuitry and synaptic connectivity remote to a thoracic SCI, supporting a role for retrograde transport of NT-3 as a potential therapeutic strategy for SCI.

scholarly journals Syringomyelia in demyelinating disease of the central nervous system: Report of two cases

2011 ◽  
Vol 139 (9-10) ◽  
pp. 657-660 ◽  
Author(s):  
Dejan Savic ◽  
Slobodan Vojinovic ◽  
Mirjana Spasic ◽  
Zoran Peric ◽  
Stevo Lukic
Keyword(s):  
Multiple Sclerosis ◽  
Spinal Cord ◽  
Central Nervous System ◽  
Nervous System ◽  
Magnetic Resonance ◽  
Demyelinating Disease ◽  
Clinical Signs ◽  
Thoracic Spinal Cord ◽  
Thoracic Spinal ◽  
The Central Nervous System

Introduction. Syringomyelia is a cavitary extension inside the spinal cord which can be either symptomatic or congenitally-idiopathic. Syringomyelia during the course of the disease in patients presenting with clinically definite multiple sclerosis was described earlier. Syringomyelia in patients presenting with a clinically isolated syndrome suggestive of multiple sclerosis is unusual. Case Outline. We present two patients presenting with demy-elinating disease of the central nervous system with syringomyelia in the cervical and thoracic spinal cord. We did not find classical clinical signs of syringomyelia in our patients, but we disclosed syringomyelia incidentally during magnetic resonance exploration. Magnetic resonance exploration using the gadolinium contrast revealed the signs of active demyelinating lesions in the spinal cord in one patient but not in the other. Conclusion. Syringomyelia in demyelinating disease of the central nervous system opens the question whether it is a coincidental finding or a part of clinical features of the disease. Differentiation of the significance of syringomyelia finding in these patients plays a role in the choice of treatment concept in such patients.

scholarly journals RGMa inhibition promotes axonal growth and recovery after spinal cord injury

2006 ◽  
Vol 173 (1) ◽  
pp. 47-58 ◽  
Author(s):  
Katsuhiko Hata ◽  
Masashi Fujitani ◽  
Yuichi Yasuda ◽  
Hideo Doya ◽  
Tomoko Saito ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Axonal Growth ◽  
Axonal Guidance ◽  
Neural Tube Closure ◽  
Cns Injury ◽  
Thoracic Spinal Cord ◽  
Thoracic Spinal ◽  
Cord Injury

Repulsive guidance molecule (RGM) is a protein implicated in both axonal guidance and neural tube closure. We report RGMa as a potent inhibitor of axon regeneration in the adult central nervous system (CNS). RGMa inhibits mammalian CNS neurite outgrowth by a mechanism dependent on the activation of the RhoA–Rho kinase pathway. RGMa expression is observed in oligodendrocytes, myelinated fibers, and neurons of the adult rat spinal cord and is induced around the injury site after spinal cord injury. We developed an antibody to RGMa that efficiently blocks the effect of RGMa in vitro. Intrathecal administration of the antibody to rats with thoracic spinal cord hemisection results in significant axonal growth of the corticospinal tract and improves functional recovery. Thus, RGMa plays an important role in limiting axonal regeneration after CNS injury and the RGMa antibody offers a possible therapeutic agent in clinical conditions characterized by a failure of CNS regeneration.

Alteration of posttraumatic ischemia in experimental spinal cord trauma by a central nervous system depressant

1979 ◽  
Vol 50 (2) ◽  
pp. 207-216 ◽  
Author(s):  
Howard J. Senter ◽  
Joan L. Venes ◽  
John S. Kauer
Keyword(s):  
Spinal Cord ◽  
Central Nervous System ◽  
Blood Flow ◽  
Nervous System ◽  
Thoracic Spinal Cord ◽  
Content Type ◽  
Thoracic Spinal ◽  
Gamma Hydroxybutyrate ◽  
Central Nervous System Depressant ◽  
Experimental Injury

✓ Blood flow after severe experimental injury to the thoracic spinal cord was studied in cats, using a modification of the hydrogen clearance technique. Gamma hydroxybutyrate, a central nervous system depressant, was shown to markedly alter the ischemic response to injury if given during the early posttraumatic period. Other vasoactive drugs investigated had no effect on posttraumatic ischemia. Therapeutic intervention during the early posttraumatic period aimed at increasing blood flow while decreasing the metabolic requirements of the injured cord may prove of value in reversing or limiting some elements of long-tract dysfunction due to the secondary ischemic insult.

Activation of spinal cord serotonergic neurons accompanies cold-induced sympathoexcitation

1994 ◽  
Vol 72 (8) ◽  
pp. 884-892 ◽  
Author(s):  
Alicia M. Passerin ◽  
William N. Henley
Keyword(s):  
Spinal Cord ◽  
Nervous System ◽  
Sympathetic Nervous System ◽  
Synthesis Inhibitor ◽  
Serotonergic Neurons ◽  
Thoracic Spinal Cord ◽  
Thoracic Spinal ◽  
Hydroxyindoleacetic Acid ◽  
Dopa Accumulation ◽  
Sympathetic Nervous

These studies examined the hypothesis that serotonergic neurons located in central sites known to be involved with autonomic regulation are activated by cold exposure, a potent stimulator of the sympathetic nervous system. In all experiments, rats were exposed to either 3 °C or 22 °C for 24 h. Significant increases (p < 0.05) in urinary norepinephrine excretion, depletions of myocardial norepinephrine, and enhanced myocardial L-DOPA accumulation following decarboxylase inhibition provided evidence of sympathoexcitation at 3 °C. Accumulations of the serotonin metabolite 5-hydroxyindoleacetic acid, in saline-injected rats, and 5-hydroxytryptophan in decarboxylase-inhibited rats were increased in spinal cord and brainstem regions of cold-exposed rats. Two hours after injection of the serotonin synthesis inhibitor p-chlorophenylalanine, significantly greater depletions of serotonin in spinal cord and 5-hydroxyindoleacetic acid in spinal cord and brainstem of cold-exposed rats were noted; synthesis inhibition also caused a larger drop in body temperature in cold-exposed rats. Microdissections of raphe nuclei and thoracic spinal cord sites indicated that the principal sites of serotonergic activation were the dorsal and intermediate spinal regions, and the raphe magnus. Thus, cold-induced sympathoexcitation was accompanied by activation of serotonergic neurons in spinal cord and brainstem regions known to be involved in autonomic regulation.Key words: serotonin, cold, stress, sympathetic nervous system, spinal cord.

Spontaneous Herniation of the Thoracic Spinal Cord: A Case Report

2001 ◽  
Vol 45 (4) ◽  
pp. 353 ◽  
Author(s):  
Sung Chan Jin ◽  
Seoung Ro Lee ◽  
Dong Woo Park ◽  
Kyung Bin Joo
Keyword(s):  
Spinal Cord ◽  
Case Report ◽  
Thoracic Spinal Cord ◽  
Thoracic Spinal ◽  
Spontaneous Herniation

Lipomeningocele associated with diplomyelia in a dog

2018 ◽  
Vol 46 (05) ◽  
pp. 323-329 ◽  
Author(s):  
Nele Ondreka ◽  
Sara Malberg ◽  
Emma Laws ◽  
Martin Schmidt ◽  
Sabine Schulze
Keyword(s):  
Spinal Cord ◽  
Neurological Status ◽  
Split Cord Malformation ◽  
Lumbar Spinal Cord ◽  
Histopathological Diagnosis ◽  
Type I ◽  
Thoracic Spinal Cord ◽  
Thoracic Spinal ◽  
Subcutaneous Mass ◽  
Lumbar Spinal

SummaryA 2-year-old male neutered mixed breed dog with a body weight of 30 kg was presented for evaluation of a soft subcutaneous mass on the dorsal midline at the level of the caudal thoracic spine. A further clinical sign was intermittent pain on palpation of the area of the subcutaneous mass. The owner also described a prolonged phase of urination with repeated interruption and re-initiation of voiding. The findings of the neurological examination were consistent with a lesion localization between the 3rd thoracic and 3rd lumbar spinal cord segments. Magnetic resonance imaging revealed a spina bifida with a lipomeningocele and diplomyelia (split cord malformation type I) at the level of thoracic vertebra 11 and 12 and secondary syringomyelia above the aforementioned defects in the caudal thoracic spinal cord. Surgical resection of the lipomeningocele via a hemilaminectomy was performed. After initial deterioration of the neurological status postsurgery with paraplegia and absent deep pain sensation the dog improved within 2 weeks to non-ambulatory paraparesis with voluntary urination. Six weeks postoperatively the dog was ambulatory, according to the owner. Two years after surgery the owner recorded that the dog showed a normal gait, a normal urination and no pain. Histopathological diagnosis of the biopsied material revealed a lipomeningocele which confirmed the radiological diagnosis.

scholarly journals The Histopathology of Severe Graded Compression in Lower Thoracic Spinal Cord Segment of Rat, Evaluated at Late Post-injury Phase

2021 ◽  
Author(s):  
Fedorova Jana ◽  
Kellerova Erika ◽  
Bimbova Katarina ◽  
Pavel Jaroslav
Keyword(s):  
Spinal Cord ◽  
Spontaneous Recovery ◽  
Traumatic Injury ◽  
Blue Dye ◽  
Post Injury ◽  
Thoracic Spinal Cord ◽  
Thoracic Spinal ◽  
Severe Traumatic Injury ◽  
Spinal Cord Segment ◽  
Cord Injury

AbstractSpontaneous recovery of lost motor functions is relative fast in rodent models after inducing a very mild/moderate spinal cord injury (SCI), and this may complicate a reliable evaluation of the effectiveness of potential therapy. Therefore, a severe graded (30 g, 40 g and 50 g) weight-compression SCI at the Th9 spinal segment, involving an acute mechanical impact followed by 15 min of persistent compression, was studied in adult female Wistar rats. Functional parameters, such as spontaneous recovery of motor hind limb and bladder emptying function, and the presence of hematuria were evaluated within 28 days of the post-traumatic period. The disruption of the blood-spinal cord barrier, measured by extravasated Evans Blue dye, was examined 24 h after the SCI, when maximum permeability occurs. At the end of the survival period, the degradation of gray and white matter associated with the formation of cystic cavities, and quantitative changes of glial structural proteins, such as GFAP, and integral components of axonal architecture, such as neurofilaments and myelin basic protein, were evaluated in the lesioned area of the spinal cord. Based on these functional and histological parameters, and taking the animal’s welfare into account, the 40 g weight can be considered as an upper limit for severe traumatic injury in this compression model.

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