Motoneuron axon pathfinding errors in zebrafish: Differential effects related to concentration and timing of nicotine exposure
| Autor: | Surangi N. Perera, Kurt R. Svoboda, Evdokia Menelaou, Latoya T. Paul |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
Nervous system
Nicotine Time Factors Genotype animal diseases Receptors Nicotinic embryonic spinal cord Toxicology Nervous System Article Animals Genetically Modified 03 medical and health sciences 0302 clinical medicine Morphogenesis medicine Animals Nicotinic Agonists Axon Zebrafish axonal pathfinding 030304 developmental biology Motor Neurons Pharmacology 0303 health sciences Dose-Response Relationship Drug biology muscle degeneration Anatomy Zebrafish Proteins biology.organism_classification Spinal cord Axons dual labeling nervous system diseases Cell biology Phenotype medicine.anatomical_structure Nicotinic agonist nervous system Larva Axon guidance Biomarkers 030217 neurology & neurosurgery Acetylcholine medicine.drug |
| Zdroj: | Toxicology and applied pharmacology |
| ISSN: | 0041-008X |
| Popis: | Nicotine exposure during embryonic stages of development can affect many neurodevelopmental processes. In the developing zebrafish, exposure to nicotine was reported to cause axonal pathfinding errors in the later born secondary motoneurons (SMNs). These alterations in SMN axon morphology coincided with muscle degeneration at high nicotine concentrations (15–30 μM). Previous work showed that the paralytic mutant zebrafish known as sofa potato exhibited nicotine-induced effects onto SMN axons at these high concentrations but in the absence of any muscle deficits, indicating that pathfinding errors could occur independent of muscle effects. In this study, we used varying concentrations of nicotine at different developmental windows of exposure to specifically isolate its effects onto subpopulations of motoneuron axons. We found that nicotine exposure can affect SMN axon morphology in a dose-dependent manner. At low concentrations of nicotine, SMN axons exhibited pathfinding errors, in the absence of any nicotine-induced muscle abnormalities. Moreover, the nicotine exposure paradigms used affected the 3 subpopulations of SMN axons differently, but the dorsal projecting SMN axons were primarily affected. We then identified morphologically distinct pathfinding errors that best described the nicotine-induced effects on dorsal projecting SMN axons. To test whether SMN pathfinding was potentially influenced by alterations in the early born primary motoneuron (PMN), we performed dual labeling studies, where both PMN and SMN axons were simultaneously labeled with antibodies. We show that only a subset of the SMN axon pathfinding errors coincided with abnormal PMN axonal targeting in nicotine-exposed zebrafish. We conclude that nicotine exposure can exert differential effects depending on the levels of nicotine and developmental exposure window. |
| Databáze: | OpenAIRE |
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