Expression of apoptosis signal-regulating kinase 1 in mouse spinal cord under chronic mechanical compression: possible involvement of the stress-activated mitogen-activated protein kinase pathways in spinal cord cell apoptosis.
METHODS
To examine apoptosis signal cascade in neurons and oligodendrocytes under the chronic spinal cord compression of tiptoe-walking Yoshimura (TWY) mouse, which is model of progressive cervical cord compression.


OBJECTIVE
To clarify the biologic mechanisms of apoptosis, which may produce destructive changes in the spinal cord under chronic mechanical compression, with a resulting irreversible neurologic deficit.


BACKGROUND
The stress-activated mitogen-activated protein kinase pathways including ASK1 transmitted apoptosis signals after acute spinal cord injury. Apoptosis in acute spinal cord injury induced both secondary degeneration around the site of injury and chronic demyelination. Chronic spinal cord compression showed myelin destruction, loss of axons, and oligodendrocytes in white matter, and loss of neurons in gray matter. Apoptosis associated with chronic spinal cord compression contributes to these changes. However, the biologic mechanisms of apoptosis in the spinal cord under chronic mechanical compression remain unclear.


METHODS
We examined the expression of phosphorylated-apoptosis signal-regulating kinase 1 (ASK1), phosphorylated-c-Jun N-terminal kinase (JNK), phosphorylated-p38 mitogen-activated protein kinase (p38), and activated caspase-3 immunohistologically in TWY mice, an animal model of progressive cervical spinal cord compression, since the ASK1-JNK and -p38 signaling cascades participate in the signaling pathway leading to apoptosis in neural tissue and neuronal culture.


RESULTS
Double immunohistochemistry for phosphorylated-ASK1, phosphorylated-JNK, phosphorylated-p38, activated-caspase3, and cell-specific markers confirmed the presence of apoptosis signals in both neurons and oligodendrocytes in compressed spinal cord cells.


CONCLUSIONS
We found that mitogen-activated protein kinase pathways including ASK1, JNK, and p38 were activated in destructive spinal cord under chronic compression.
Takenouchi
Takeshi
T
Department of Orthopaedic Surgery, Graduated School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan.
Setoguchi
Takao
T
Yone
Kazunori
K
Komiya
Setsuro
S
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology*; D048848:MAP Kinase Kinase Kinase 5 / Q000096:biosynthesis* / Q000235:genetics; D020935:MAP Kinase Signaling System / Q000502:physiology*; D051379:Mice; D008813:Mice, Inbred ICR; D008818:Mice, Neurologic Mutants; D013116:Spinal Cord / Q000201:enzymology* / Q000473:pathology; D013117:Spinal Cord Compression / Q000201:enzymology* / Q000235:genetics / Q000473:pathology*; D013314:Stress, Mechanical
D048848:MAP Kinase Kinase Kinase 5