The extracellular matrix glycoprotein tenascin-C promotes locomotor recovery after spinal cord injury in adult zebrafish.
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The extracellular matrix glycoprotein tenascin-C promotes locomotor recovery after spinal cord injury in adult zebrafish. / Yu, Y-M; Cristofanilli, M; Valiveti, A; Ma, L; Yoo, M; Morellini, Fabio; Schachner, Melitta.
In: NEUROSCIENCE, Vol. 183, 2011, p. 238-250.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - The extracellular matrix glycoprotein tenascin-C promotes locomotor recovery after spinal cord injury in adult zebrafish.
AU - Yu, Y-M
AU - Cristofanilli, M
AU - Valiveti, A
AU - Ma, L
AU - Yoo, M
AU - Morellini, Fabio
AU - Schachner, Melitta
PY - 2011
Y1 - 2011
N2 - Adult zebrafish, by virtue of exhibiting spontaneous recovery after spinal lesion, have evolved into a paradigmatic vertebrate model system to identify novel genes vital for successful regeneration after spinal cord injury. Due to a remarkable level of conservation between zebrafish and human genomes, such genes, once identified, could point to possibilities for addressing the multiple issues on how to deal with functional recovery after spinal cord injury in humans. In the current study, the extracellular matrix glycoprotein tenascin-C was studied in the zebrafish spinal cord injury model to assess the often disparate functions of this multidomain molecule under in vivo conditions. This in vivo study was deemed necessary since in vitro studies had shown discrepant functional effects on neurite outgrowth: tenascin-C inhibits neurite outgrowth when presented as a molecular barrier adjacent to a conducive substrate, but enhances neurite outgrowth when presented as a uniform substrate. Thus, our current study addresses the question as to which of these features prevails in vivo: whether tenascin-C reduces or enhances axonal regrowth after injury in a well accepted vertebrate model of spinal cord injury. We show upregulation of tenascin-C expression in regenerating neurons of the nucleus of median longitudinal fascicle (NMLF) in the brainstem and spinal motoneurons. Inhibition of tenascin-C expression by antisense oligonucleotide (morpholino) resulted in impaired locomotor recovery, reduced regrowth of axons from brainstem neurons and reduced synapse formation by the regrowing brainstem axons on spinal motoneurons, all vital indicators of regeneration. Our results thus point to an advantageous role of tenascin-C in promoting spinal cord regeneration, by promoting axonal regrowth and synapse formation in the spinal cord caudal to the lesion site after injury.
AB - Adult zebrafish, by virtue of exhibiting spontaneous recovery after spinal lesion, have evolved into a paradigmatic vertebrate model system to identify novel genes vital for successful regeneration after spinal cord injury. Due to a remarkable level of conservation between zebrafish and human genomes, such genes, once identified, could point to possibilities for addressing the multiple issues on how to deal with functional recovery after spinal cord injury in humans. In the current study, the extracellular matrix glycoprotein tenascin-C was studied in the zebrafish spinal cord injury model to assess the often disparate functions of this multidomain molecule under in vivo conditions. This in vivo study was deemed necessary since in vitro studies had shown discrepant functional effects on neurite outgrowth: tenascin-C inhibits neurite outgrowth when presented as a molecular barrier adjacent to a conducive substrate, but enhances neurite outgrowth when presented as a uniform substrate. Thus, our current study addresses the question as to which of these features prevails in vivo: whether tenascin-C reduces or enhances axonal regrowth after injury in a well accepted vertebrate model of spinal cord injury. We show upregulation of tenascin-C expression in regenerating neurons of the nucleus of median longitudinal fascicle (NMLF) in the brainstem and spinal motoneurons. Inhibition of tenascin-C expression by antisense oligonucleotide (morpholino) resulted in impaired locomotor recovery, reduced regrowth of axons from brainstem neurons and reduced synapse formation by the regrowing brainstem axons on spinal motoneurons, all vital indicators of regeneration. Our results thus point to an advantageous role of tenascin-C in promoting spinal cord regeneration, by promoting axonal regrowth and synapse formation in the spinal cord caudal to the lesion site after injury.
KW - Animals
KW - Humans
KW - Disease Models, Animal
KW - Analysis of Variance
KW - Cell Count
KW - Motor Activity/drug effects
KW - RNA, Messenger/metabolism
KW - Neural Pathways/pathology
KW - Choline O-Acetyltransferase/metabolism
KW - Brain Stem/pathology
KW - Indoles/diagnostic use
KW - Lysine/analogs & derivatives/metabolism
KW - Membrane Glycoproteins/metabolism
KW - Motor Neurons/metabolism
KW - Nerve Regeneration/drug effects
KW - Oligodeoxyribonucleotides, Antisense/therapeutic use
KW - Recovery of Function/drug effects/physiology
KW - Spinal Cord Injuries/drug therapy/metabolism/pathology/physiopathology
KW - Synapses/pathology
KW - Tenascin/genetics/metabolism
KW - Transcription Factors/metabolism
KW - Up-Regulation/drug effects/physiology
KW - Zebrafish
KW - Zebrafish Proteins/metabolism
KW - Animals
KW - Humans
KW - Disease Models, Animal
KW - Analysis of Variance
KW - Cell Count
KW - Motor Activity/drug effects
KW - RNA, Messenger/metabolism
KW - Neural Pathways/pathology
KW - Choline O-Acetyltransferase/metabolism
KW - Brain Stem/pathology
KW - Indoles/diagnostic use
KW - Lysine/analogs & derivatives/metabolism
KW - Membrane Glycoproteins/metabolism
KW - Motor Neurons/metabolism
KW - Nerve Regeneration/drug effects
KW - Oligodeoxyribonucleotides, Antisense/therapeutic use
KW - Recovery of Function/drug effects/physiology
KW - Spinal Cord Injuries/drug therapy/metabolism/pathology/physiopathology
KW - Synapses/pathology
KW - Tenascin/genetics/metabolism
KW - Transcription Factors/metabolism
KW - Up-Regulation/drug effects/physiology
KW - Zebrafish
KW - Zebrafish Proteins/metabolism
M3 - SCORING: Journal article
VL - 183
SP - 238
EP - 250
JO - NEUROSCIENCE
JF - NEUROSCIENCE
SN - 0306-4522
ER -