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HSP90 and pCREB alterations are linked to mancozeb‐dependent behavioral and neurodegenerative effects in a marine teleost

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ABSTRACT The pesticide mancozeb (mz) is recognized as a potent inducer of oxidative stress due to its ability to catalyze the production of reactive oxygen species plus inhibiting mitochondrial respiration… Click to show full abstract

ABSTRACT The pesticide mancozeb (mz) is recognized as a potent inducer of oxidative stress due to its ability to catalyze the production of reactive oxygen species plus inhibiting mitochondrial respiration thus becoming an environmental risk for neurodegenerative diseases. Despite numerous toxicological studies on mz have been directed to mammals, attention on marine fish is still lacking. Thus, it was our intention to evaluate neurobehavioral activities of ornate wrasses (Thalassoma pavo) exposed to 0.2 mg/l of mz after a preliminary screening test (0.07–0.3 mg/l). Treated fish exhibited an evident (p < 0.001) latency to reach T‐maze arms (> 1000%) while exploratory attitudes (total arm entries) diminished (− 50%; p < 0.05) versus controls during spontaneous exploration tests. Moreover, they showed evident enhancements (+ 111%) of immobility in the cylinder test. Contextually, strong (− 88%; p < 0.01) reductions of permanence in light zone of the Light/Dark apparatus along with diminished crossings (− 65%) were also detected. Conversely, wrasses displayed evident enhancements (160%) of risk assessment consisting of fast entries in the dark side of this apparatus. From a molecular point of view, a notable activation (p < 0.005) of the brain transcription factor pCREB occurred during mz‐exposure. Similarly, in situ hybridization supplied increased HSP90 mRNAs in most brain areas such as the lateral part of the dorsal telencephalon (Dl; + 68%) and valvula of the cerebellum (VCe; + 35%) that also revealed evident argyrophilic signals. Overall, these first indications suggest a possible protective role of the early biomarkers pCREB and HSP90 against fish toxicity. HIGHLIGHTSFish exposed to mancozeb exhibited an evident latency to reach T‐maze arms.Mancozeb caused immobility and reduction of explorative attitudes.Fish exposed to mancozeb showed anxiogenic performances in the Light/Dark apparatus.The brain of fish exposed to mancozeb supplied pCREB plus HSP90 mRNA up‐regulations.Some brain areas of fish exposed to mancozeb revealed an evident neurodegeneration.

Keywords: pcreb alterations; hsp90 pcreb; exposed mancozeb; fish exposed; brain

Journal Title: Toxicology and Applied Pharmacology
Year Published: 2017

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