scholarly journals Alterations of Dopamine-Related Transcripts in A11 Diencephalospinal Pathways after Spinal Cord Injury

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Shunyi Zhao ◽  
Jaclyn H. DeFinis ◽  
Shaoping Hou
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Primary Source ◽  
D1 Receptors ◽  
Spinal Cord Tissue ◽  
Mrna Levels ◽  
Spinal Segment ◽  
Adult Rats ◽  
Cord Injury ◽  
The Brain

The diencephalic A11 nuclei are the primary source of spinal dopamine (DA). Neurons in this region project to all levels of the spinal cord. Traumatic spinal cord injury (SCI) often interrupts descending and ascending neuronal pathways and further elicits injury-induced neuronal plasticity. However, it is unknown how A11 neurons and projections respond to SCI-induced axotomy. Based on preliminary observation, we hypothesized that A11 DA-ergic neurons rostral to the lesion site might change their capacity to synthesize DA after SCI. Adult rats received a complete spinal cord transection at the 10th thoracic (T10) level. After 3 or 8 weeks, rostral (T5) and caudal (L1) spinal cord tissue was collected to measure mRNA levels of DA-related genes. Meanwhile, A11 neurons in the brain were explicitly isolated by laser capture microdissection, and single-cell qPCR was employed to evaluate mRNA levels in the soma. Histological analysis was conducted to assess the number of A11 DA-ergic neurons. The results showed that, compared to naïve rats, mRNA levels of tyrosine hydroxylase (TH), dopamine decarboxylase (DDC), and D2 receptors in the T5 spinal segment had a transient decrease and subsequent recovery. However, dopamine-β-hydroxylase (DBH), D1 receptors, and DA-associated transcription factors did not change following SCI. Furthermore, axon degeneration below the lesion substantially reduced mRNA levels of TH and D2 in the L1 spinal segment. However, DDC transcript underwent only a temporary decrease. Similar mRNA levels of DA-related enzymes were detected in the A11 neuronal soma between naïve and SCI rats. In addition, immunostaining revealed that the number of A11 DA neurons did not change after SCI, indicating a sustention of capacity to synthesize DA in the neuroplasm. Thus, impaired A11 diencephalospinal pathways following SCI may transiently reduce DA production in the spinal cord rostral to the lesion but not in the brain.

scholarly journals Ascorbic Acid Promotes Functional Restoration after Spinal Cord Injury Partly by Epigenetic Modulation

Cells ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 1310 ◽  
Author(s):  
Jin Young Hong ◽  
Ganchimeg Davaa ◽  
Hyunjin Yoo ◽  
Kwonho Hong ◽  
Jung Keun Hyun
Keyword(s):  
Spinal Cord ◽  
Dna Methylation ◽  
Spinal Cord Injury ◽  
Ascorbic Acid ◽  
Motor Cortex ◽  
Functional Restoration ◽  
Mrna Levels ◽  
Cord Injury ◽  
Epigenetic Modulation ◽  
The Brain

Axonal regeneration after spinal cord injury (SCI) is difficult to achieve, and no fundamental treatment can be applied in clinical settings. DNA methylation has been suggested to play a role in regeneration capacity and neuronal growth after SCI by controlling the expression of regeneration-associated genes (RAGs). The aim of this study was to examine changes in neuronal DNA methylation status after SCI and to determine whether modulation of DNA methylation with ascorbic acid can enhance neuronal regeneration or functional restoration after SCI. Changes in epigenetic marks (5-hydroxymethylcytosine (5hmC) and 5-methylcytosine (5mC)); the expression of Ten-eleven translocation (Tet) family genes; and the expression of genes related to inflammation, regeneration, and degeneration in the brain motor cortex were determined following SCI. The 5hmC level within the brain was increased after SCI, especially in the acute and subacute stages, and the mRNA levels of Tet gene family members (Tet1, Tet2, and Tet3) were also increased. Administration of ascorbic acid (100 mg/kg) to SCI rats enhanced 5hmC levels; increased the expression of the Tet1, Tet2, and Tet3 genes within the brain motor cortex; promoted axonal sprouting within the lesion cavity of the spinal cord; and enhanced recovery of locomotor function until 12 weeks. In conclusion, we found that epigenetic status in the brain motor cortex is changed after SCI and that epigenetic modulation using ascorbic acid may contribute to functional recovery after SCI.

scholarly journals Exercise Ameliorates Spinal Cord Injury by Changing DNA Methylation

Cells ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 143
Author(s):  
Ganchimeg Davaa ◽  
Jin Young Hong ◽  
Tae Uk Kim ◽  
Seong Jae Lee ◽  
Seo Young Kim ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Motor Cortex ◽  
Functional Recovery ◽  
Treadmill Exercise ◽  
Exercise Group ◽  
Control Group ◽  
Epigenetic Changes ◽  
Cord Injury ◽  
The Brain

Exercise training is a traditional method to maximize remaining function in patients with spinal cord injury (SCI), but the exact mechanism by which exercise promotes recovery after SCI has not been identified; whether exercise truly has a beneficial effect on SCI also remains unclear. Previously, we showed that epigenetic changes in the brain motor cortex occur after SCI and that a treatment leading to epigenetic modulation effectively promotes functional recovery after SCI. We aimed to determine how exercise induces functional improvement in rats subjected to SCI and whether epigenetic changes are engaged in the effects of exercise. A spinal cord contusion model was established in rats, which were then subjected to treadmill exercise for 12 weeks. We found that the size of the lesion cavity and the number of macrophages were decreased more in the exercise group than in the control group after 12 weeks of injury. Immunofluorescence and DNA dot blot analysis revealed that levels of 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) in the brain motor cortex were increased after exercise. Accordingly, the expression of ten-eleven translocation (Tet) family members (Tet1, Tet2, and Tet3) in the brain motor cortex also elevated. However, no macrophage polarization was induced by exercise. Locomotor function, including Basso, Beattie, and Bresnahan (BBB) and ladder scores, also improved in the exercise group compared to the control group. We concluded that treadmill exercise facilitates functional recovery in rats with SCI, and mechanistically epigenetic changes in the brain motor cortex may contribute to exercise-induced improvements.

scholarly journals Spinal Cord Injury Increases Pro-inflammatory Cytokine Expression in Kidney at Acute and Sub-chronic Stages

Inflammation ◽  
2021 ◽  
Author(s):  
Shangrila Parvin ◽  
Clintoria R. Williams ◽  
Simone A. Jarrett ◽  
Sandra M. Garraway
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Inflammatory Response ◽  
Inflammatory Cytokine ◽  
Cardiovascular Health ◽  
Mrna Levels ◽  
Post Injury ◽  
Cord Injury ◽  
And Function ◽  
The Impact

Abstract— Accumulating evidence supports that spinal cord injury (SCI) produces robust inflammatory plasticity. We previously showed that the pro-inflammatory cytokine tumor necrosis factor (TNF)α is increased in the spinal cord after SCI. SCI also induces a systemic inflammatory response that can impact peripheral organ functions. The kidney plays an important role in maintaining cardiovascular health. However, SCI-induced inflammatory response in the kidney and the subsequent effect on renal function have not been well characterized. This study investigated the impact of high and low thoracic (T) SCI on C-fos, TNFα, interleukin (IL)-1β, and IL-6 expression in the kidney at acute and sub-chronic timepoints. Adult C57BL/6 mice received a moderate contusion SCI or sham procedures at T4 or T10. Uninjured mice served as naïve controls. mRNA levels of the proinflammatory cytokines IL-1β, IL-6, TNFα, and C-fos, and TNFα and C-fos protein expression were assessed in the kidney and spinal cord 1 day and 14 days post-injury. The mRNA levels of all targets were robustly increased in the kidney and spinal cord, 1 day after both injuries. Whereas IL-6 and TNFα remained elevated in the spinal cord at 14 days after SCI, C-fos, IL-6, and TNFα levels were sustained in the kidney only after T10 SCI. TNFα protein was significantly upregulated in the kidney 1 day after both T4 and T10 SCI. Overall, these results clearly demonstrate that SCI induces robust systemic inflammation that extends to the kidney. Hence, the presence of renal inflammation can substantially impact renal pathophysiology and function after SCI.

Spinal Cord Tissue Bridges Validation Study: Predictive Relationships With Sensory Scores Following Cervical Spinal Cord Injury

2021 ◽  
Author(s):  
Andrew C. Smith ◽  
Denise R. O’Dell ◽  
Wesley A. Thornton ◽  
David Dungan ◽  
Eli Robinson ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
External Validation ◽  
Inpatient Rehabilitation ◽  
Spinal Cord Tissue ◽  
Light Touch ◽  
Post Injury ◽  
Data Set ◽  
Cord Injury ◽  
Predictive Relationships

Background: Using magnetic resonance imaging (MRI), widths of ventral tissue bridges demonstrated significant predictive relationships with future pinprick sensory scores, and widths of dorsal tissue bridges demonstrated significant predictive relationships with future light touch sensory scores, following spinal cord injury (SCI). These studies involved smaller participant numbers, and external validation of their findings is warranted. Objectives: The purpose of this study was to validate these previous findings using a larger independent data set. Methods: Widths of ventral and dorsal tissue bridges were quantified using MRI in persons post cervical level SCI (average 3.7 weeks post injury), and pinprick and light touch sensory scores were acquired at discharge from inpatient rehabilitation (average 14.3 weeks post injury). Pearson product-moments were calculated and linear regression models were created from these data. Results: Wider ventral tissue bridges were significantly correlated with pinprick scores (r = 0.31, p < 0.001, N = 136) and wider dorsal tissue bridges were significantly correlated with light touch scores (r = 0.31, p < 0.001, N = 136) at discharge from inpatient rehabilitation. Conclusion: This retrospective study’s results provide external validation of previous findings, using a larger sample size. Following SCI, ventral tissue bridges hold significant predictive relationships with future pinprick sensory scores and dorsal tissue bridges hold significant predictive relationships with future light touch sensory scores.

Time-dependent progression of neurogenic lower urinary tract dysfunction after spinal cord injury in the mouse model

2021 ◽  
Author(s):  
Tetsuichi Saito ◽  
Daisuke Gotoh ◽  
Naoki Wada ◽  
Pradeep Tyagi ◽  
Tomonori Minagawa ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Time Course ◽  
Time Dependent ◽  
Lower Urinary Tract Dysfunction ◽  
Emg Activity ◽  
Mrna Levels ◽  
Mechanosensitive Channels ◽  
Reduction Time ◽  
Cord Injury

This study evaluated the time-course changes in bladder and external urinary sphincter (EUS) activity as well as the expression of mechanosensitive channels in lumbosacral dorsal root ganglia (DRG) after spinal cord injury (SCI). Female C57BL/6N mice in the SCI group underwent transection of the Th8/9 spinal cord. Spinal intact mice and SCI mice at 2, 4 and 6 weeks post SCI were evaluated by single-filling cystometry and EUS-electromyography (EMG). In another set of mice, the bladder and L6-S1 DRG were harvested for protein and mRNA analyses. In SCI mice, non-voiding contractions was confirmed at 2 weeks post-SCI, and did not increase over time to 6 weeks. In 2-weeks SCI mice, EUS-EMG measurements revealed detrusor-sphincter dyssynergia (DSD), but periodic EMG reductions during bladder contraction were hardly observed. At 4 weeks, SCI mice showed increases of EMG activity reduction time with increased voiding efficiency (VE). At 6 weeks, SCI mice exhibited a further increase in EMG reduction time. RT-PCR of L6-S1 DRG showed increased mRNA levels of TRPV1 and ASIC1-3 in SCI mice with a decrease of ASIC2-3 at 6 weeks compared to 4 weeks whereas Piezo2 showed a slow increase at 6 weeks. Protein assay showed the SCI-induced overexpression of bladder BDNF with a time-dependent decrease post SCI. These results indicate that detrusor overactivity is established in the early phase whereas DSD is completed later at 4 weeks with an improvement at 6 weeks post SCI, and that mechanosensitive channels may be involved in the time-dependent changes.

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