Minocycline alleviates death of oligodendrocytes by inhibiting pro-nerve growth factor production in microglia after spinal cord injury

Tae Y. Yune, Jee Y. Lee, Gil Y. Jung, Sun J. Kim, Mei H. Jiang, Young C. Kim, Young J. Oh, George J. Markelonis, Tae H. Oh

Research output: Contribution to journalArticle

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Abstract

Spinal cord injury (SCI) causes a permanent neurological disability, and no satisfactory treatment is currently available. After SCI, pro-nerve growth factor (proNGF) is known to play a pivotal role in apoptosis of oligodendrocytes, but the cell types producing proNGF and the signaling pathways involved in proNGF production are primarily unknown. Here, we show that minocycline improves functional recovery after SCI in part by reducing apoptosis of oligodendrocytes via inhibition of proNGF production in microglia. After SCI, the stress-responsive p38 mitogen-activated protein kinase (p38MAPK) was activated only in microglia, and proNGF was produced by microglia via the p38MAPK-mediated pathway. Minocycline treatment significantly reduced proNGF production in microglia in vitro and in vivo by inhibition of the phosphorylation of p38MAPK. Furthermore, minocycline treatment inhibited p75 neurotrophin receptor expression and RhoA activation after injury. Finally, minocycline treatment inhibited oligodendrocyte death and improved functional recovery after SCI. These results suggest that minocycline may represent a potential therapeutic agent for acute SCI in humans.

Original languageEnglish
Pages (from-to)7751-7761
Number of pages11
JournalJournal of Neuroscience
Volume27
Issue number29
DOIs
Publication statusPublished - 2007 Jul 18

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Minocycline
Oligodendroglia
Microglia
Nerve Growth Factor
Spinal Cord Injuries
p38 Mitogen-Activated Protein Kinases
Apoptosis
Nerve Growth Factor Receptor
Phosphorylation
Wounds and Injuries

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

Cite this

Yune, Tae Y. ; Lee, Jee Y. ; Jung, Gil Y. ; Kim, Sun J. ; Jiang, Mei H. ; Kim, Young C. ; Oh, Young J. ; Markelonis, George J. ; Oh, Tae H. / Minocycline alleviates death of oligodendrocytes by inhibiting pro-nerve growth factor production in microglia after spinal cord injury. In: Journal of Neuroscience. 2007 ; Vol. 27, No. 29. pp. 7751-7761.
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Minocycline alleviates death of oligodendrocytes by inhibiting pro-nerve growth factor production in microglia after spinal cord injury. / Yune, Tae Y.; Lee, Jee Y.; Jung, Gil Y.; Kim, Sun J.; Jiang, Mei H.; Kim, Young C.; Oh, Young J.; Markelonis, George J.; Oh, Tae H.

In: Journal of Neuroscience, Vol. 27, No. 29, 18.07.2007, p. 7751-7761.

Research output: Contribution to journalArticle

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T1 - Minocycline alleviates death of oligodendrocytes by inhibiting pro-nerve growth factor production in microglia after spinal cord injury

AU - Yune, Tae Y.

AU - Lee, Jee Y.

AU - Jung, Gil Y.

AU - Kim, Sun J.

AU - Jiang, Mei H.

AU - Kim, Young C.

AU - Oh, Young J.

AU - Markelonis, George J.

AU - Oh, Tae H.

PY - 2007/7/18

Y1 - 2007/7/18

N2 - Spinal cord injury (SCI) causes a permanent neurological disability, and no satisfactory treatment is currently available. After SCI, pro-nerve growth factor (proNGF) is known to play a pivotal role in apoptosis of oligodendrocytes, but the cell types producing proNGF and the signaling pathways involved in proNGF production are primarily unknown. Here, we show that minocycline improves functional recovery after SCI in part by reducing apoptosis of oligodendrocytes via inhibition of proNGF production in microglia. After SCI, the stress-responsive p38 mitogen-activated protein kinase (p38MAPK) was activated only in microglia, and proNGF was produced by microglia via the p38MAPK-mediated pathway. Minocycline treatment significantly reduced proNGF production in microglia in vitro and in vivo by inhibition of the phosphorylation of p38MAPK. Furthermore, minocycline treatment inhibited p75 neurotrophin receptor expression and RhoA activation after injury. Finally, minocycline treatment inhibited oligodendrocyte death and improved functional recovery after SCI. These results suggest that minocycline may represent a potential therapeutic agent for acute SCI in humans.

AB - Spinal cord injury (SCI) causes a permanent neurological disability, and no satisfactory treatment is currently available. After SCI, pro-nerve growth factor (proNGF) is known to play a pivotal role in apoptosis of oligodendrocytes, but the cell types producing proNGF and the signaling pathways involved in proNGF production are primarily unknown. Here, we show that minocycline improves functional recovery after SCI in part by reducing apoptosis of oligodendrocytes via inhibition of proNGF production in microglia. After SCI, the stress-responsive p38 mitogen-activated protein kinase (p38MAPK) was activated only in microglia, and proNGF was produced by microglia via the p38MAPK-mediated pathway. Minocycline treatment significantly reduced proNGF production in microglia in vitro and in vivo by inhibition of the phosphorylation of p38MAPK. Furthermore, minocycline treatment inhibited p75 neurotrophin receptor expression and RhoA activation after injury. Finally, minocycline treatment inhibited oligodendrocyte death and improved functional recovery after SCI. These results suggest that minocycline may represent a potential therapeutic agent for acute SCI in humans.

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