Early suppression of the endocannabinoid degrading enzymes FAAH and MAGL alters locomotor development in zebrafish
| Autor: | M. Ruhul Amin, M. Shah Sufian, Declan W. Ali |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Physiology
Aquatic Science Amidohydrolases chemistry.chemical_compound Fatty acid amide hydrolase medicine Animals Molecular Biology Zebrafish Ecology Evolution Behavior and Systematics JZL184 Chemistry Motor neuron URB597 Endocannabinoid system Monoacylglycerol Lipases 3. Good health Cell biology Monoacylglycerol lipase Nicotinic acetylcholine receptor medicine.anatomical_structure nervous system Insect Science lipids (amino acids peptides and proteins) Animal Science and Zoology JZL195 Endocannabinoids |
| Zdroj: | Journal of Experimental Biology. 224 |
| ISSN: | 1477-9145 0022-0949 |
| DOI: | 10.1242/jeb.242635 |
| Popis: | The fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL) enzymes are the predominant catabolic regulators of the major endocannabinoids (eCBs) anadamide (AEA) and 2-arachidonoylglycerol (2-AG), respectively. The expression and roles of eCBs during early embryogenesis remain to be fully investigated. Here, we inhibited FAAH and MAGL in zebrafish embryos during the first 24 h of life and examined motor neuron and locomotor development at 2 and 5 days post fertilization (dpf). Application of the dual FAAH/MAGL inhibitor, JZL195 (2 µmol l−1), resulted in a reduction in primary and secondary motor neuron axonal branching. JZL195 also reduced nicotinic acetylcholine receptor (nAChR) expression at neuromuscular junctions. Application of URB597 (5 µmol l−1), a specific inhibitor of the FAAH enzyme, also decreased primary motor neuron branching but did not affect secondary motor neuron branching and nAChR expression. Interestingly, JZL184 (5 µmol l−1), a specific inhibitor of MAGL, showed no effects on motor neuron branching or nAChR expression. Co-treatment of the enzyme inhibitors with the CB1R inhibitor AM251 confirmed the involvement of CB1R in motor neuron branching. Disruption of FAAH or MAGL reduced larval swimming activity, and AM251 attenuated the JZL195- and URB597-induced locomotor changes, but not the effects of JZL184. Together, these findings indicate that inhibition of FAAH, or augmentation of AEA acting through CB1R during early development, may be responsible for locomotor deficiencies. |
| Databáze: | OpenAIRE |
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