Effects of endocrine disruptors on the electrical activity of leptin receptor neurons in the dorsomedial hypothalamus and anxiety-like behavior in male mice

Yavuz Y., Ozen D. O., Erol Z. Y., Goren H., Yilmaz B.

Environmental Pollution, vol.324, 2023 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 324
  • Publication Date: 2023
  • Doi Number: 10.1016/j.envpol.2023.121366
  • Journal Name: Environmental Pollution
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, PASCAL, Aerospace Database, Aqualine, Aquatic Science & Fisheries Abstracts (ASFA), BIOSIS, Biotechnology Research Abstracts, CAB Abstracts, Chemical Abstracts Core, Chimica, Communication Abstracts, Compendex, EMBASE, Environment Index, Food Science & Technology Abstracts, Geobase, Greenfile, MEDLINE, Metadex, Pollution Abstracts, Veterinary Science Database, Civil Engineering Abstracts
  • Keywords: Anxiety-like behavior, Electrophysiology, Leptin receptor neurons, Locomotor activity, p,p'-DDT, TBT
  • Dokuz Eylül University Affiliated: No

Abstract

There is increasing concern about the effects of endocrine disrupting chemicals (EDCs) on human health. Recently, some EDCs are suggested to affect energy metabolism leading to increased risk of obesity. Obesogenic effects of some EDCs on adipogenesis have been reported, however, there is no study examining their potential actions on the brain circuits controlling feeding and metabolism. We have investigated effects of tributyltin (TBT) and dichlorodiphenyltrichloroethane (p,p'-DDT) on electrical activity on dorsomedial hypothalamic leptin receptor neurons (DMHLepR), morphological adaptations in neuronal anatomy of DMHLepR, locomotion, and anxiety-like behaviors in mice. Twenty-three Lep-Cre transgenic mice were intracranially injected with GFP virus. Control animals received intraperitoneal corn oil alone while group 2 and 3 received TBT (25 μg/kg) and p,p'-DDT (2 mg/kg) for one month. Locomotor activity and anxiety-like behavior of the animals were determined by open field test. Electrophysiological effects of TBT and p,p'-DDT on DMHLepR neurons were determined by patch clamp method. Neuronal anatomy was determined by confocal microscopy. Spontaneous firing frequency of DMHLepR neurons of TBT group of mice was significantly higher than both p,p'-DDT and control groups (p < 0.01). TBT and p,p'-DDT significantly decreased frequency of the spontaneous inhibitory post-synaptic currents to DMHLepR neurons compared to the control group (p < 0.05). The time spent in the center and the number of entrances to the center by the TBT-administered mice were significantly lower than other groups (p < 0.01). The total distance traveled and mean speed of the control group of mice were significantly higher than the p,p'-DDT- and TBT-administered animals (p < 0.0001). c-Fos activity of the p,p'-DDT- and TBT-administered animals were significantly elevated compared to the control group (p < 0.001), while no change in the number of dendritic spines were observed. In conclusion, this study demonstrates that exposure to TBT and p,p'-DDT alters electrical activity in DMHLepR neurons and behavioral state in mice.