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 ◽  
...  

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.

2018 ◽  
Author(s):  
Daniel Sobrido-Cameán ◽  
Diego Robledo ◽  
Laura Sánchez ◽  
María Celina Rodicio ◽  
Antón Barreiro-Iglesias

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.


2019 ◽  
Vol 12 (2) ◽  
pp. dmm037085 ◽  
Author(s):  
Daniel Sobrido-Cameán ◽  
Diego Robledo ◽  
Laura Sánchez ◽  
María Celina Rodicio ◽  
Antón Barreiro-Iglesias

2017 ◽  
Vol 2017 ◽  
pp. 1-12 ◽  
Author(s):  
Antón Barreiro-Iglesias ◽  
Daniel Sobrido-Cameán ◽  
Michael I. Shifman

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.


2018 ◽  
Vol 9 (6) ◽  
Author(s):  
Daniel Romaus-Sanjurjo ◽  
Rocío Ledo-García ◽  
Blanca Fernández-López ◽  
Kendra Hanslik ◽  
Jennifer R. Morgan ◽  
...  

2006 ◽  
Author(s):  
Mark I. Tonack ◽  
Sander L. Hitzig ◽  
B. Catharine Craven ◽  
Kent A. Campbell ◽  
Kathryn A. Boschen ◽  
...  

Author(s):  
Khaled Hassan

This Pilot retrospective research conducted on the results of open surgery in patients with Grade III and IV haemorrhoids With SCI. No major complications had arisen at 6 weeks post-operative and all wounds had healed, but 1 patient Anal fissure recurrence. 75% of patients reported a substantial increase in anorectal anorexia during long-term follow-up. With symptoms. Five patients reported recurrences: three haemorrhoids (18 percent) and two anal fissures (25 percent).   Keywords: Haemorrhoids, Pilot retrospective research, Anorectal Anorexia.


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