A Small Organic Compound Mimicking the L1 Cell Adhesion Molecule Promotes Functional Recovery after Spinal Cord Injury in Zebrafish
Authors: Melitta Schachner
Yanqin Shen
Zhihua Zhang
Junkai Hu
Sudhanshu Sahu
Gabriele Loers
Huifan Shen
Rong Li
Journal: Molecular Neurobiology (2018)
Discipline: NEUROSCIENCE & BEHAVIOR
Keywords: Axonal regrowth; Cell adhesion molecule L1; Spinal cord injury; Tacrine; Zebrafish.
Affiliations: Center for Neuroscience, Shantou University Medical College, 22 Xin Ling Road, Shantou, Guangdong, 515041, China., Center for Neuroscience, Shantou University Medical College, 22 Xin Ling Road, Shantou, Guangdong, 515041, China. ., Medical School, Jiangnan University, 1800 Li Hu Road, Wuxi, Jiangsu, 214122, China. ., Keck Center for Collaborative Neuroscience and Department of Cell Biology and Neuroscience, Rutgers University, Piscataway, NJ, 08554, USA. .

Abstract:  Tacrine is a small organic compound that was discovered to mimic the functions of the neural cell adhesion molecule L1 by promoting the cognate functions of L1 in vitro, such as neuronal survival, neuronal migration, neurite outgrowth, and myelination. Based on studies indicating that L1 enhances functional recovery in different central and peripheral nervous system disease paradigms of rodents, it deemed interesting to investigate the beneficial role of tacrine in the attractive zebrafish animal model, by evaluating functional recovery after spinal cord injury. To this aim, larval and adult zebrafish were exposed to tacrine treatment after spinal cord injury and monitored for locomotor recovery and axonal regrowth. Tacrine promoted the rapid recovery of locomotor activities in both larval and adult zebrafish, enhanced regrowth of severed axons and myelination, and reduced astrogliosis in the spinal cords. Tacrine treatment upregulated the expression of L1.1 (a homolog of the mammalian recognition molecule L1) and enhanced the L1.1-mediated intracellular signaling cascades in the injured spinal cords. These observations lead to the hope that, in combination with other therapeutic approaches, this old drug may become a useful reagent to ameliorate the deficits resulting from acute and chronic injuries of the mammalian nervous system. 

Retracted: No

PubPeer comments:
 In figure 6B of this paper, a panel has been duplicated. 6Bb is supposed to show Biocytin-labeled axons at 10 days after SCI without tacrine treatment, 6Be is supposed to show Biocytin-labeled axons at 10 days after SCI with tacrine treatment. They are the same section with the red channel removed in 6Be, but should be from different animals.  , 
 Looking at this paper further, there are a number of bands that look very similar. In particular, in Figure 7, the control bands for the blots in 7C, D, E, and F (boxed in red below) appear identical. This could be explained if this was the same gel that had been stripped, but this is unlikely. If you look at 7C, the p-ERK and ERK1 2 bands are essentially the same molecular weight as the control protein, but the slant of the individual bands is very different.  The control band in 7B is a different one (boxed in green). This looks virtually identical in 9B and 9C. There is one band in particular (10 days post SCI) that has compression artefacts around it (arrow). Again, the shape width slant of the PTEN and p53 bands are very different from their corresponding control bands, so unlikely to have been run on the same gel.  Finally, something odd is going on in Figure 9A - this figure seems a bit stretched, but its control lane is very similar to 7C-F. I have copied the control lane from figure 7D below and pulled it out to illustrate the similaritty. Once pulled apart, the font also fits with 9A. Interestingly, if you turn that image 180 degrees, the shape of the bands looks quite a lot like those in CK2alpha lane.  ,