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A Neurosphere Assay to Evaluate Endogenous Neural Stem Cell Activation in a Mouse Model of Minimal Spinal Cord Injury
Published on: September 13, 2018
Serine-threonine protein kinase activation may be an effective target for reducing neuronal apoptosis after spinal
Mu Jin1, Yan-Wei Yang1, Wei-Ping Cheng1
1Department of Anesthesiology, Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing, China.
Abstract:
The signaling mechanisms underlying ischemia-induced nerve cell apoptosis are poorly understood. We investigated the effects of apoptosis-related signal transduction pathways following ischemic spinal cord injury, including extracellular signal-regulated kinase (ERK), serine-threonine protein kinase (Akt) and c-Jun N-terminal kinase (JNK) signaling pathways. We established a rat model of acute spinal cord injury by inserting a catheter balloon in the left subclavian artery for 25 minutes. Rat models exhibited notable hindlimb dysfunction. Apoptotic cells were abundant in the anterior horn and central canal of the spinal cord. The number of apoptotic neurons was highest 48 hours post injury. The expression of phosphorylated Akt (p-Akt) and phosphorylated ERK (p-ERK) increased immediately after reperfusion, peaked at 4 hours (p-Akt) or 2 hours (p-ERK), decreased at 12 hours, and then increased at 24 hours. Phosphorylated JNK expression reduced after reperfusion, increased at 12 hours to near normal levels, and then showed a downward trend at 24 hours. Pearson linear correlation analysis also demonstrated that the number of apoptotic cells negatively correlated with p-Akt expression. These findings suggest that activation of Akt may be a key contributing factor in the delay of neuronal apoptosis after spinal cord ischemia, particularly at the stage of reperfusion, and thus may be a target for neuronal protection and reduction of neuronal apoptosis after spinal cord injury.
Insights
Activation of Akt signaling may protect nerve cells from apoptosis after spinal cord ischemia. This finding suggests Akt activation is a potential therapeutic target for reducing neuronal cell death following spinal cord injury.
Area of Science:
- Neuroscience
- Cellular Biology
- Biochemistry
Background:
- Spinal cord injury (SCI) triggers nerve cell apoptosis, but the underlying signaling mechanisms remain unclear.
- Understanding these pathways is crucial for developing neuroprotective strategies.
Purpose of the Study:
- To investigate the roles of extracellular signal-regulated kinase (ERK), serine-threonine protein kinase (Akt), and c-Jun N-terminal kinase (JNK) signaling pathways in apoptosis following ischemic SCI.
- To determine the correlation between these signaling pathways and neuronal apoptosis.
Main Methods:
- An acute ischemic spinal cord injury rat model was established using a catheter balloon.
- Hindlimb dysfunction and apoptotic cell counts were assessed.
- Expression levels of phosphorylated Akt (p-Akt), phosphorylated ERK (p-ERK), and phosphorylated JNK were measured at various time points post-injury.
- Pearson linear correlation analysis was used to evaluate relationships between apoptotic cells and signaling molecules.
Main Results:
- Ischemic SCI induced significant hindlimb dysfunction and widespread neuronal apoptosis, peaking at 48 hours post-injury.
- p-Akt and p-ERK expression initially increased post-reperfusion, with distinct temporal patterns.
- p-JNK expression initially decreased then recovered towards baseline levels.
- A negative correlation was observed between the number of apoptotic cells and p-Akt expression.
Conclusions:
- Akt activation appears to play a protective role in delaying neuronal apoptosis after spinal cord ischemia, especially during reperfusion.
- Targeting Akt signaling may offer a promising therapeutic approach for neuroprotection and reducing neuronal loss in SCI.
