Neurofilament proteins in axonal regeneration and neurodegenerative diseases

Neurofilament protein is a component of the mature neuronal cytoskeleton, and it interacts with the zygosome, which is mediated by neurofilament-related proteins. Neurofilament protein regulates enzyme function and the structure of linker proteins. In addition, neurofilament gene expression plays an important role in nervous system development. Previous studies have shown that neurofilament gene transcriptional regulation is crucial for neurofilament protein expression, especially in axonal regeneration and degenerative diseases. Post-transcriptional regulation increased neurofilament protein gene transcription during axonal regeneration, ultimately resulting in a pattern of neurofilament protein expression. An expression imbalance of post-transcriptional regulatory proteins and other disorders could lead to amyotrophic lateral sclerosis or other neurodegenerative diseases. These findings indicated that after transcription, neurofilament protein regulated expression of related proteins and promoted regeneration of damaged axons, suggesting that regulation disorders could lead to neurodegenerative diseases.

Stress protein expression in early phase spinal cord ischemia/reperfusion injury

Spinal cord ischemia/reperfusion injury is a stress injury to the spinal cord. Our previous studies using differential proteomics identified 21 differentially expressed proteins （n 〉 2） in rabbits with spinal cord ischemia/reperfusion injury. Of these proteins, stress-related proteins included protein disulfide isomerase A3, stress-induced-phosphoprotein 1 and heat shock cognate protein 70. In this study, we established New Zealand rabbit models of spinal cord ischemia/reperfusion injury by abdominal aorta occlusion. Results demonstrated that hind limb function initially improved after spinal cord ischemia/reperfusion injury, but then deteriorated. The pathological morphology of the spinal cord became aggravated, but lessened 24 hours after reperfusion. However, the numbers of motor neurons and interneurons in the spinal cord gradually decreased. The expression of protein disulfide isomerase A3, stress-induced-phosphoprotein 1 and heat shock cognate protein 70 was induced by ischemia/reperfusion injury. The expression of these proteins increased within 12 hours after reperfusion, and then decreased, reached a minimum at 24 hours, but subsequently increased again to similar levels seen at 6-12 hours, showing a characterization of induction-inhibition-induc- tion. These three proteins were expressed only in cytoplasm but not in the nuclei. Moreover, the expression was higher in interneurons than in motor neurons, and the survival rate of interneurons was greater than that of motor neurons. It is assumed that the expression of stress-related proteins exhibited a protective effect on neurons.

Electrical stimulation of the sacral nerve anterior root following induced bladder detrusor contraction

The sacral nerve anterior root consists of parasympathetic nerves（dominating urinary bladder detrusor）and somatic motor nerves（dominating urethral sphincter）,and electrical stimulation to the sacral nerve anterior root induces simultaneous contraction of the bladder detrusor and urethral sphincter.Accordingly,urethral pressure exceeds intravesical pressure,resulting in little or no urination,kidney damage,and trembling of lower limbs due to high intravesical pressure.In the present study,sacral nerve posterior roots were transected in a spastic bladder rabbit model,followed by three-pole electrode and long-pulse electrical stimulation to the sacral anterior root.Intravesical and urethral pressures were simultaneously measured to verify the feasibility of anode inhibition to the sacral anterior root following induced detrusor contraction.As stimulus intensity increased,somatic motor nerves were increasingly inhibited; with a stimulus pulse width of 300 μs and stimulus current of 1.05 mA,urethral pressure was zero and average intravesical pressure was 3.84 kPa.In addition,detrusor contraction was displayed,and lower extremity trembling was significantly reduced.Three-pole electrode and long-pulse electrical stimulation to the sacral nerve anterior root induced detrusor contraction and inhibited low extremity trembling under electrical stimulation.

Differential protein expression in spinal cord tissue of a rabbit model of spinal cordischemia/reperfusion injury

New Zealand rabbits were randomly divided into an ischemia group （occlusion of the abdominal aorta for 60 minutes）, an ischemia-reperfusion group （occlusion of the abdominal aorta for 60 minutes followed by 48 hours of reperfusion） and a sham-surgery group. Two-dimensional gel electrophoresis detected 49 differentially expressed proteins in spinal cord tissue from the ischemia and ischemia/ reperfusion groups and 23 of them were identified by mass spectrometry. In the ischemia group, the expression of eight proteins was up regulated, and that of the remaining four proteins was down regulated. In the ischemia/reperfusion group, the expression of four proteins was up regulated, and that of two proteins was down regulated. In the sham-surgery group, only one protein was detected. In the ischemia and ischemia/reperfusion groups, four proteins overlapped between groups with the same differential expression, including three that were up regulated and one down regulated. These proteins were related to energy metabolism, cell defense, inflammatory mechanism and cell signaling.

Factors affecting directional migration of bone marrow mesenchymal stem cells to the injured spinal cord

Microtubule-associated protein 1B plays an important role in axon guidance and neuronal migration. In the present study, we sought to discover the mechanisms underlying microtu- bule-associated protein 1B mediation of axon guidance and neuronal migration. We exposed bone marrow mesenchymal stem cells to okadaic acid or N-acetyl-D-erythro-sphingosine （an inhibitor and stimulator, respectively, of protein phosphatase 2A） for 24 hours. The expression of the phosphorylated form of type I microtubule-associated protein 1B in the cells was greater after exposure to okadaic acid and lower after N-acetyl-D-erythro-sphingosine. We then injected the bone marrow mesenchymal stem cells through the ear vein into rabbit models of spinal cord contusion. The migration of bone marrow mesenchymal stem cells towards the injured spinal cord was poorer in cells exposed to okadaic acid- and N-acetyl-D-erythro-sphingosine than in non-treated bone marrow mesenchymal stem cells. Finally, we blocked phosphatidylinosi- tol 3-kinase （PI3K） and extracellular signal-regulated kinase 1/2 （ERK1/2） pathways in rabbit bone marrow mesenchymal stem cells using the inhibitors LY294002 and U0126, respectively. LY294002 resulted in an elevated expression of phosphorylated type I microtubule-associated protein 1B, whereas U0126 caused a reduction in expression. The present data indicate that PI3K and ERKI/2 in bone marrow mesenchymal stem cells modulate the phosphorylation of micro- tubule-associated protein 1B via a cross-signaling network, and affect the migratory efficiency of bone marrow mesenchymal stem cells towards injured spinal cord.

Effects of cytokines and chemokines on migration of mesenchymal stem cells following spinal cord injury

We investigated the effects of cytokines and chemokines and their associated signaling pathways on mesenchymal stem cell migration after spinal cord injury, to determine their roles in the curative effects of mesenchymal stem cells. This study reviewed the effects of tumor necrosis factor-α, vascular endothelial growth factor, hepatocyte growth factor, platelet-derived growth factor, basic fibroblast growth factor, insulin like growth factor-I, stromal cell-derived factor and monocyte chemoattractant protein-1, 3 during mesenchymal stem cell migration to damaged sites, and analyzed the signal transduction pathways involved in their effects on mesenchymal stem cell migration. The results confirmed that phosphatidylinositol 3-kinase/serine/threonine protein kinases and nuclear factor-KB play crucial roles in the migration of mesenchymal stem cells induced by cytokines and chemokines.

The role of microtubule-associated protein 1B in axonal growth and neuronal migration in the central nervous system

In this review, we discuss the role of microtubule-associated protein 1 B （MAP1B） and its phosphorylation in axonal development and regeneration in the central nervous system. MAP1B exhibits similar functions during axonal development and regeneration. MAP1B and phosphorylated MAPIB in neurons and axons maintain a dynamic balance between cytoskeletal components, and regulate the stability and interaction of microtubules and actin to promote axonal growth, neural connectivity and regeneration in the central nervous system.