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The Adhesion Molecule-Characteristic HNK-1 Carbohydrate Contributes to Functional Recovery After Spinal Cord Injury in Adult Zebrafish

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Abstract

The human natural killer cell antigen-1 (HNK-1) is functionally important in development, synaptic activity, and regeneration after injury in the nervous system of several mammalian species. It contains a sulfated glucuronic acid which is carried by neural adhesion molecules and expressed in nonmammalian species, including zebrafish, which, as opposed to mammals, spontaneously regenerate after injury in the adult. To evaluate HNK-1’s role in recovery of function after spinal cord injury (SCI) of adult zebrafish, we assessed the effects of the two HNK-1 synthesizing enzymes, glucuronyl transferase and HNK-1 sulfotransferase. Expression of these two enzymes was increased at the messenger RNA (mRNA) level 11 days after injury in the brainstem nuclei that are capable of regrowth of severed axons, namely, the nucleus of medial longitudinal fascicle and intermediate reticular formation, but not at earlier time points after SCI. mRNA levels of glucuronyl transferase and sulfotransferase were increased in neurons, not only of these nuclei but also in the spinal cord caudal to the injury site at 11 days. Mauthner neurons which are not capable of regeneration did not show increased levels of enzyme mRNAs after injury. Reducing protein levels of the enzymes by application of anti-sense morpholinos resulted in reduction of locomotor recovery for glucuronyl transferase, but not for HNK-1 sulfotransferase. The combined results indicate that HNK-1 is upregulated in expression only in those neurons that are intrinsically capable of regeneration and contributes to regeneration after spinal cord injury in adult zebrafish in the absence of its sulfate moiety.

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Abbreviations

GlcAT-P:

HNK-1 glucuronyl transferase

HMGB1:

High mobility group box 1

HNK-1:

Human natural killer cell antigen-1

HNK-1ST:

HNK-1 sulfotransferase

IMRF:

Intermediate reticular formation

MAG:

Myelin-associated glycoprotein

MO:

Morpholino

NMLF:

Nucleus of the medial longitudinal fascicle

SCI:

Spinal cord injury

SGGL:

Sulfoglucuronylglycolipids

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Authors and Affiliations

  1. Keck Center for Collaborative Neuroscience and Department of Cell Biology and Neuroscience, Rutgers University, 604 Allison Road, Piscataway, NJ, 08854, USA

    Liping Ma & Melitta Schachner

  2. Center for Neuroscience, Shantou University Medical College, 22 Xin Ling Road, Shantou, Guangdong, 515041, P.R. China

    Hui-Fan Shen, Yan-Qin Shen & Melitta Schachner

  3. Department of Basic Medicine, Jiangnan University Medical School, Wuxi, Jiangsu, P.R. China

    Yan-Qin Shen

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  1. Liping Ma
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Correspondence to Melitta Schachner.

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Ma, L., Shen, HF., Shen, YQ. et al. The Adhesion Molecule-Characteristic HNK-1 Carbohydrate Contributes to Functional Recovery After Spinal Cord Injury in Adult Zebrafish. Mol Neurobiol 54, 3253–3263 (2017). https://doi.org/10.1007/s12035-016-9876-4

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