scholarly journals Serotonin inhibits axonal regeneration of identifiable descending neurons after a complete spinal cord injury in lampreys

2019 ◽  
Vol 12 (2) ◽  
pp. dmm037085 ◽  
Author(s):  
Daniel Sobrido-Cameán ◽  
Diego Robledo ◽  
Laura Sánchez ◽  
María Celina Rodicio ◽  
Antón Barreiro-Iglesias
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Axonal Regeneration ◽  
Descending Neurons ◽  
Cord Injury ◽  
Complete Spinal Cord Injury

scholarly journals Serotonin inhibits axonal regeneration of identifiable descending neurons after a complete spinal cord injury in lampreys

2018 ◽  
Author(s):  
Daniel Sobrido-Cameán ◽  
Diego Robledo ◽  
Laura Sánchez ◽  
María Celina Rodicio ◽  
Antón Barreiro-Iglesias
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Axonal Regeneration ◽  
Axonal Guidance ◽  
Descending Neurons ◽  
Expression Of Genes ◽  
Subsequent Decrease ◽  
Cord Injury ◽  
Key Factor ◽  
Complete Spinal Cord Injury

SummaryClassical neurotransmitters are mainly known for their roles as neuromodulators, but they also play important roles in the control of developmental and regenerative processes. Here, we used the lamprey model of spinal cord injury to study the effect of serotonin in axon regeneration at the level of individually identifiable descending neurons. Pharmacological and genetic treatments after a complete spinal cord injury showed that endogenous serotonin inhibits axonal regeneration in identifiable descending neurons through the activation of serotonin 1A receptors and a subsequent decrease in cAMP levels. RNA sequencing revealed that changes in the expression of genes that control axonal guidance could be a key factor on the serotonin effects during regeneration. This study provides new targets of interest for research in non-regenerating mammalian models of traumatic CNS injuries and extends the known roles of serotonin signalling during neuronal regeneration.

scholarly journals Taurine promotes axonal regeneration after a complete spinal cord injury in lampreys

IBRO Reports ◽  
2019 ◽  
Vol 6 ◽  
pp. S507-S508
Author(s):  
Antón Barreiro-Iglesias ◽  
Daniel Sobrido-Cameán ◽  
Blanca Fernández-López ◽  
Natividad Pereiro ◽  
Anunciación Lafuente ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Axonal Regeneration ◽  
Cord Injury ◽  
Complete Spinal Cord Injury

scholarly journals Retrograde Activation of the Extrinsic Apoptotic Pathway in Spinal-Projecting Neurons after a Complete Spinal Cord Injury in Lampreys

2017 ◽  
Vol 2017 ◽  
pp. 1-12 ◽  
Author(s):  
Antón Barreiro-Iglesias ◽  
Daniel Sobrido-Cameán ◽  
Michael I. Shifman
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Molecular Mechanisms ◽  
Extrinsic Pathway ◽  
Apoptotic Pathway ◽  
Permanent Disability ◽  
Descending Neurons ◽  
Neuronal Soma ◽  
Cord Injury ◽  
Complete Spinal Cord Injury

Spinal cord injury (SCI) is a devastating condition that leads to permanent disability because injured axons do not regenerate across the trauma zone to reconnect to their targets. A prerequisite for axonal regeneration will be the prevention of retrograde degeneration that could lead to neuronal death. However, the specific molecular mechanisms of axotomy-induced degeneration of spinal-projecting neurons have not been elucidated yet. In lampreys, SCI induces the apoptotic death of identifiable descending neurons that are “bad regenerators/poor survivors” after SCI. Here, we investigated the apoptotic process activated in identifiable descending neurons of lampreys after SCI. For this, we studied caspase activation by using fluorochrome-labeled inhibitors of caspases, the degeneration of spinal-projecting neurons using Fluro-Jade C staining, and the involvement of the intrinsic apoptotic pathway by means of cytochrome c and Vαdouble immunofluorescence. Our results provide evidence that, after SCI, bad-regenerating spinal cord-projecting neurons slowly degenerate and that the extrinsic pathway of apoptosis is involved in this process. Experiments using the microtubule stabilizer Taxol showed that caspase-8 signaling is retrogradely transported by microtubules from the site of axotomy to the neuronal soma. Preventing the activation of this process could be an important therapeutic approach after SCI in mammals.

scholarly journals GABA promotes survival and axonal regeneration in identifiable descending neurons after spinal cord injury in larval lampreys

2018 ◽  
Vol 9 (6) ◽  
Author(s):  
Daniel Romaus-Sanjurjo ◽  
Rocío Ledo-García ◽  
Blanca Fernández-López ◽  
Kendra Hanslik ◽  
Jennifer R. Morgan ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Axonal Regeneration ◽  
Descending Neurons ◽  
Cord Injury

scholarly journals Taurine promotes axonal regeneration after a complete spinal cord injury in lampreys

2019 ◽  
Author(s):  
Daniel Sobrido-Cameán ◽  
Blanca Fernández-López ◽  
Natividad Pereiro ◽  
Anunciación Lafuente ◽  
María Celina Rodicio ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Axonal Regeneration ◽  
Axon Regeneration ◽  
Traumatic Event ◽  
Axonal Regrowth ◽  
Cord Injury ◽  
Taurine Treatment ◽  
Complete Spinal Cord Injury ◽  
The Brain

AbstractTaurine is one of the most abundant free amino acids in the brain. It is well known that taurine protects the brain from further damage after a traumatic event. However, only a few ex vivo studies have looked at the possible role of taurine in the regulation of axon regeneration after injury. Here, we aimed to reveal the possible role for taurine in the modulation of axonal regeneration following a complete spinal cord injury (SCI) using lampreys as an animal model. The brainstem of lampreys contains several individually identifiable descending neurons that differ greatly in their capacity for axonal regeneration after SCI. This offers a convenient model to promote or inhibit axonal regrowth in the same in vivo preparation. First, we carried out high performance liquid chromatography experiments to measure taurine levels in the spinal cord following SCI. Our results revealed a statistically significant increase in taurine levels 4 weeks post lesion, which suggested that taurine might have a positive effect on axonal regrowth. Based on these results, we decided to apply an acute taurine treatment at the site of injury to study its effect on axon regeneration. Results from these experiments show that an acute taurine treatment enhances axonal regeneration following SCI in lampreys. This offers a novel way to try to promote axon regeneration after nervous system injuries in mammalian models.

scholarly journals GABA promotes survival and axonal regeneration in identifiable descending neurons after spinal cord injury in larval lampreys

2018 ◽  
Author(s):  
D Romaus-Sanjurjo ◽  
R Ledo-García ◽  
B Fernández-López ◽  
K Hanslik ◽  
JR Morgan ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Axonal Regeneration ◽  
Gabab Receptor ◽  
Gabab Receptors ◽  
Regenerative Capacity ◽  
Permanent Disability ◽  
Descending Neurons ◽  
Cord Injury

AbstractIn mammals, spinal cord injury (SCI) causes permanent disability. The poor regenerative capacity of descending neurons is one of the main causes of the lack of recovery after SCI. In addition, the prevention of retrograde degeneration leading to the atrophy or death of descending neurons is an obvious prerequisite for the activation of axonal regeneration. Lampreys show an amazing regenerative capacity after SCI. Recent histological work in lampreys suggested that GABA, which is massively released after a SCI, could promote the survival of descending neurons. Here, we aimed to study if GABA, acting through GABAB receptors, promotes the survival and axonal regeneration of descending neurons of larval sea lampreys after a complete SCI. First, we used in situ hybridization to confirm that identifiable descending neurons of late stage larvae express the gabab1 subunit of the sea lamprey GABAB receptor. We also observed an acute increase in the expression of this subunit in descending neurons after a complete SCI, which further supported the possible role of GABA and GABAB receptors in promoting the survival and regeneration of these neurons. So, we performed gain and loss of function experiments to confirm this hypothesis. Treatments with GABA and baclofen (GABAB agonist) significantly reduced caspase activation in descending neurons 2 weeks after a complete SCI. Long-term treatments with GABOB (a GABA analogue) and baclofen significantly promoted axonal regeneration of descending neurons after SCI. These data indicate that GABAergic signalling through GABAB receptors promotes the survival and regeneration of descending neurons after SCI. Finally, we used morpholinos against the gabab1 subunit to specifically knockdown the expression of the GABAB receptor in descending neurons. Long-term morpholino treatments caused a significant inhibition of axonal regeneration, which shows that endogenous GABA promotes axonal regeneration after a complete SCI in lampreys by activating GABAB receptors expressed in descending neurons. These data implicate GABAB receptors in spinal cord regeneration in lampreys and further provide a new target of interest for SCI.

scholarly journals Taurine Promotes Axonal Regeneration after a Complete Spinal Cord Injury in Lampreys

2020 ◽  
Vol 37 (6) ◽  
pp. 899-903 ◽  
Author(s):  
Daniel Sobrido-Cameán ◽  
Blanca Fernández-López ◽  
Natividad Pereiro ◽  
Anunciación Lafuente ◽  
María Celina Rodicio ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Axonal Regeneration ◽  
Cord Injury ◽  
Complete Spinal Cord Injury
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