Overexpression of Wld(S) or Nmnat2 in mauthner cells by single-cell electroporation delays axon degeneration in live zebrafish.
Axon degeneration is supposed to be a therapeutic target for treating neurodegenerative diseases. Mauthner cells (M-cells) are ideal for studying axons in vivo because of their limited numbers, large size, and long axons. In this study, we labeled M-cells by single-cell electroporation with plasmids expressing DsRed2 or EGFP. Injury-induced axon degeneration in labeled M-cell was imaged under a confocal microscope, and we found that the Mauthner axons started to degenerate about 24 hr after lesion. The Wld(S) protein containing full-length Nmnat1 is well-known for its axon-protective function in many systems. Overexpression of Wld(S) in M-cells also greatly delayed axon degeneration in live zebrafish. Nmnat2 is the only Nmnat highly expressed in brain. Here we demonstrated that overexpression of Nmnat2 in M-cells significantly delayed axon degeneration in vivo, and disruption of the NAD synthesis activity of Nmnat2 markedly attenuated its axon-protective function. All these data show that injury-induced axon degeneration of M-cell has a mechanism similar to that in mammalians and would be a valuable model for studying axon degeneration in vivo.
Feng
Yan
Y
Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai, China.
Yan
Tingting
T
Zheng
Jin
J
Ge
Xinjian
X
Mu
Yu
Y
Zhang
Yi
Y
Wu
Dongmei
D
Du
Jiu-Lin
JL
Zhai
Qiwei
Q
D000818:Animals; D001369:Axons / Q000378:metabolism* / Q000473:pathology; D018274:Electroporation; D057809:HEK293 Cells; D006801:Humans; D047468:Immunoprecipitation; D018613:Microscopy, Confocal; D009410:Nerve Degeneration / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009612:Nicotinamide-Nucleotide Adenylyltransferase / Q000235:genetics / Q000378:metabolism*; D015027:Zebrafish
D009419:Nerve Tissue Proteins; C484008:NMNAT2 protein, human; D009612:Nicotinamide-Nucleotide Adenylyltransferase