Phenelzine, a cell adhesion molecule L1 mimetic small organic compound, promotes functional recovery and axonal regrowth in spinal cord-injured zebrafish

Adhesion Molecule L1 Agonist Mimetics Protect Against the Pesticide Paraquat-Induced Locomotor Deficits and Biochemical Alterations in Zebrafish

“…Consistent with this, a protective effect of PS has been reported for neurons and astrocytes against formaldehyde-induced neurotoxicity by reversion of decreased glutamate uptake via the second messengers Akt and p38 (Song et al, 2010). Furthermore, several lines of evidence highlight the neuroprotective effect of PS in spinal cord (Chen, Z. et al, 2016;Li et al, 2018) and traumatic brain injury (Hill et al, 2019). Tacrine (TC) (9-amino-1,2,3,4-tetrahydroacridine), a non-selective, reversible cholinesterase inhibitor, affecting acetylcholinesterase and butyrylcholinesterase, was launched as the first drug to alleviate the symptoms of Alzheimer's disease (Crismon, 1994).…”

“…For survival analysis, hatched larvae at 3 dpf without apparent abnormalities were exposed to PQ (10-5000 µM) and L1 mimetics (PS and TC) in a six-well plate (Jet Biofil, Guangzhou, China) (24 larvae/3 ml/well) until 7 dpf. The exposure tests were conducted following the OECD guidelines (OECD, 1992), the concentration range of PQ was selected based on previous studies (Imamura et al, 2011;Wang et al, 2018;Pinho et al, 2019), and for L1 mimetics (250 nM), concentration was selected for both mimetics based on their beneficial role in previous studies (Li et al, 2018;Sahu et al, 2018). In order to determine the effect of different treatments on the survival of zebrafish larvae, each concentration (10-5000 µM) of PQ alone and PQ in the presence of L1 mimetics (PS or TC) at 5 and 7 dpf were individually compared and statistically analyzed by one-way analysis of variance (ANOVA) using Tukey's post hoc test.…”

“…Stock solutions of PS and TC were dissolved in distilled water and then diluted in aquarium water to the desired concentrations. For the L1 mimetic compounds, previously reported beneficial concentrations in adult zebrafish were considered (Li et al, 2018;Sahu et al, 2018). After the acclimatization period, adult male zebrafish (0.4-0.6 g) were anesthetized by immersion in a solution of 0.033% MS222 (ethyl 3-aminobenzoate methane sulfonate) (Cat no.…”

“…The two L1 mimetic compounds PS and TC were identified by competitive enzyme-linked immunosorbent assay (ELISA) screening of NIH libraries I and II and shown to inhibit binding of the L1 function-triggering 557 monoclonal antibody reacting with the extracellular domain of L1 and to serve as L1 mimetic agonists (Kataria et al, 2016). Therefore, keeping in mind the beneficial roles of L1 and L1 mimetic compounds in other neural diseases (Kataria et al, 2016;Sytnyk et al, 2017;Xu et al, 2017;Li et al, 2018;Sahu et al, 2018), we here attempted to investigate their protective effects against PQ-induced toxicity in zebrafish, which have been well recognized as a useful animal model for other vertebrates because of its evolutionarily conserved brain functions, well-characterized neurotransmitter system, well-described behavioral patterns, and low maintenance costs (Panula et al, 2006;Flinn et al, 2008;Gerlai, 2011). We here demonstrate that the two L1 mimetics overcome PQ-induced deficits in motor and non-motor functions, thus expecting them to be potential additions to the arsenals of compounds treating PD.…”

Knockdown of chondroitin‐4‐sulfotransferase‐1, but not of dermatan‐4‐sulfotransferase‐1, accelerates regeneration of zebrafish after spinal cord injury

“…Laser-induced SCI in larval zebrafish was performed as previously described (27). This method allows for complete transection of the spinal cord (27,28). In brief, laser injury and imaging were performed with an FV1000 MPE 2-photon laser scanning microscope (Olympus, Tokyo, Japan) equipped with a femtosecond single-box Ti-sapphire oscillator (Mai Tai DeepSee; Newport Corporation, Irvine, CA, USA).…”