Concerted monoamine oxidase activity following exposure to di-2-ethylhexyl phthalate is associated with aggressive neurobehavioral response and neurodegeneration in zebrafish brain

Comp Biochem Physiol C Toxicol Pharmacol. 2024 Sep:283:109970. doi: 10.1016/j.cbpc.2024.109970. Epub 2024 Jun 27.

Abstract

Di-2-ethylhexyl phthalate (DEHP) is the most commonly preferred synthetic organic chemical in plastics and its products for making them ductile, flexible and durable. As DEHP is not chemically bound to the macromolecular polymer of plastics, it can be easily leached out to accumulate in food and environment. Our recent report advocated that exposure to DEHP significantly transformed the innate bottom-dwelling and scototaxis behaviour of zebrafish. Our present study aimed to understand the possible role of DEHP exposure pertaining towards the development of aggressive behaviour and its association with amplified monoamine oxidase activity and neurodegeneration in the zebrafish brain. As heightened monoamine oxidase (MAO) is linked with genesis of aggressive behaviour, our observation also coincides with DEHP-persuaded aggressive neurobehavioral transformation in zebrafish. Our preliminary findings also showed that DEHP epitomized as a prime factor in transforming native explorative behaviour and genesis of aggressive behaviour through oxidative stress induction and changes in the neuromorphology in the periventricular grey zone (PGZ) of the zebrafish brain. With the finding demarcating towards heightened chromatin condensation in the PGZ of zebrafish brain, our further observation by immunohistochemistry showed a profound augmentation in apoptotic cell death marker cleaved caspase 3 (CC3) expression following exposure to DEHP. Our further observation by immunoblotting study also demarcated a temporal augmentation in CC3 and tyrosine hydroxylase expression in the zebrafish brain. Therefore, the gross findings of the present study delineate the idea that chronic exposure to DEHP is associated with MAO-instigated aggressive neurobehavioral transformation and neurodegeneration in the zebrafish brain.

Keywords: Aggressive neurobehavioral response; Cleaved caspase-3; Di-2-ethylhexyl phthalate; Monoamine oxidase; Neurodegeneration; Oxidative stress.

MeSH terms

  • Aggression* / drug effects
  • Animals
  • Apoptosis / drug effects
  • Behavior, Animal* / drug effects
  • Brain* / drug effects
  • Brain* / enzymology
  • Brain* / metabolism
  • Diethylhexyl Phthalate* / toxicity
  • Monoamine Oxidase* / metabolism
  • Nerve Degeneration / chemically induced
  • Nerve Degeneration / pathology
  • Oxidative Stress / drug effects
  • Water Pollutants, Chemical / toxicity
  • Zebrafish Proteins / genetics
  • Zebrafish Proteins / metabolism
  • Zebrafish*

Substances

  • Diethylhexyl Phthalate
  • Monoamine Oxidase
  • Water Pollutants, Chemical
  • Zebrafish Proteins