The extracellular matrix glycoprotein tenascin-C is beneficial for spinal cord regeneration.
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The extracellular matrix glycoprotein tenascin-C is beneficial for spinal cord regeneration. / Chen, Jian; Lee, Hyun Joon; Jakovcevski, Igor; Shah, Ronak; Bhagat, Neha; Loers, Gabriele; Liu, Hsing-Yin; Meiners, Sally; Taschenberger, Grit; Kügler, Sebastian; Irintchev, Andrey; Schachner, Melitta.
in: MOL THER, Jahrgang 18, Nr. 10, 10, 2010, S. 1769-1777.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - The extracellular matrix glycoprotein tenascin-C is beneficial for spinal cord regeneration.
AU - Chen, Jian
AU - Lee, Hyun Joon
AU - Jakovcevski, Igor
AU - Shah, Ronak
AU - Bhagat, Neha
AU - Loers, Gabriele
AU - Liu, Hsing-Yin
AU - Meiners, Sally
AU - Taschenberger, Grit
AU - Kügler, Sebastian
AU - Irintchev, Andrey
AU - Schachner, Melitta
PY - 2010
Y1 - 2010
N2 - Tenascin-C (TNC), a major component of the extracellular matrix, is strongly upregulated after injuries of the central nervous system (CNS) but its role in tissue repair is not understood. Both regeneration promoting and inhibiting roles of TNC have been proposed considering its abilities to both support and restrict neurite outgrowth in vitro. Here, we show that spontaneous recovery of locomotor functions after spinal cord injury is impaired in adult TNC-deficient (TNC(-/-)) mice in comparison to wild-type (TNC(+/+)) mice. The impaired recovery was associated with attenuated excitability of the plantar Hoffmann reflex (H-reflex), reduced glutamatergic input, reduced sprouting of monaminergic axons in the lumbar spinal cord and enhanced post-traumatic degeneration of corticospinal axons. The degeneration of corticospinal axons in TNC(-/-) mice was normalized to TNC(+/+) levels by application of the alternatively spliced TNC fibronectin type III homologous domain D (fnD). Finally, overexpression of TNC-fnD via adeno-associated virus in wild-type mice improved locomotor recovery, increased monaminergic axons sprouting, and reduced lesion scar volume after spinal cord injury. The functional efficacy of the viral-mediated TNC indicates a potentially useful approach for treatment of spinal cord injury.
AB - Tenascin-C (TNC), a major component of the extracellular matrix, is strongly upregulated after injuries of the central nervous system (CNS) but its role in tissue repair is not understood. Both regeneration promoting and inhibiting roles of TNC have been proposed considering its abilities to both support and restrict neurite outgrowth in vitro. Here, we show that spontaneous recovery of locomotor functions after spinal cord injury is impaired in adult TNC-deficient (TNC(-/-)) mice in comparison to wild-type (TNC(+/+)) mice. The impaired recovery was associated with attenuated excitability of the plantar Hoffmann reflex (H-reflex), reduced glutamatergic input, reduced sprouting of monaminergic axons in the lumbar spinal cord and enhanced post-traumatic degeneration of corticospinal axons. The degeneration of corticospinal axons in TNC(-/-) mice was normalized to TNC(+/+) levels by application of the alternatively spliced TNC fibronectin type III homologous domain D (fnD). Finally, overexpression of TNC-fnD via adeno-associated virus in wild-type mice improved locomotor recovery, increased monaminergic axons sprouting, and reduced lesion scar volume after spinal cord injury. The functional efficacy of the viral-mediated TNC indicates a potentially useful approach for treatment of spinal cord injury.
M3 - SCORING: Zeitschriftenaufsatz
VL - 18
SP - 1769
EP - 1777
JO - MOL THER
JF - MOL THER
SN - 1525-0016
IS - 10
M1 - 10
ER -
