Anxiety Disorder is a common neurological disorder for which ubiquitous environmental endocrine disruptors may be risk factors. 17β-trenbolone (17-TB) has been recognized as a potential environmental endocrine disruptor and its neurotoxic effects have attracted attention. Tachykinin receptor 3 (TACR3), a G protein-coupled receptor involved in pubertal anxiety, and its underlying neural mechanisms remain enigmatic. Therefore, this study investigated the possible relationship between 17-TB and TACR3, testosterone (T), and synaptic plasticity. Our results showed that adolescent male Balb/c mice developed significant anxiety-like behavior after four weeks of exposure to environmentally relevant concentrations of 17-TB (100 μg/kg/day). Transcriptomic RNA-Seq results showed that 17-TB affected abnormal synaptic transmission signals in the hippocampus. Electrophysiological results showed that 17-TB reduced the activity of hippocampal dentate gyrus (DG) neurons and led to the downregulation of hippocampal TACR3 and T levels. In addition, Western blot, immunohistochemistry, ELISA, and qRT-PCR showed that 17-TB exposure led to the downregulation of key hippocampal synaptic proteins PSD95, Gephyrin, and Syn, and induced a metabolic imbalance in glutamate (Glu)/GABA signaling, affecting dopamine signaling. Interestingly, testosterone supplementation (10 mg/kg/day) was effective in ameliorating the above phenomena and alleviating anxiety-like behaviors. These results suggest that 17-TB modulates anxiety-related synaptic plasticity by regulating hippocampal TACR3 and T interactions in vivo. In conclusion, our study contributes to understanding the neurobehavioral and potential mechanistic effects of environmental 17-TB exposure in mammals. It alerts the public to the health risks of chemicals to mammals and suggests new research directions and potential therapeutic targets.
As an emerging contaminant in the environment, trenbolone (TBE) has aroused a global health crisis and caused the huge impact on ecosystem. Its sensitive detection is critical to safeguard human health and ecosystem. Herein, a photocurrent polarity switching photoelectrochemical (PEC)-electrochemical (EC) dual-mode sensing platform was presented for highly selective and sensitive detection of TBE by ingeniously tailor signal probe. The tailored Cu 2 O@CuO-hemin acting as both photocurrent polarity reversal and electroactivity factor were cross-linked with TBE-BSA to obtain competitive conjugates for TBE. When the competitive response was initiated, numerous of Cu 2 O@CuO-hemin nanocomposites are introduced on the CdS-modified indium tin oxide electrode, serving as the reporting agent of EC/PEC dual-mode assay. The photocurrent polarity of the CdS-modified ITO can be effectively switched, enabling PEC analysis of TBE with distinguishing photocurrent changes. The linear response range is 1 pg/mL to 500 ng/mL, and the detection limit is 15.0 fg/mL. Meanwhile, the Cu 2 O@CuO could triggered the amplified current variations via effectually catalyzing the H 2 O 2 decomposition compared to the CdS NPs, leading to the sensitive electrochemical detection of TBE with a detection limit 200 fg/mL and a linear response range from1 pg/mL to 500 ng/mL. Additionally, the developed sensing platform enabled mutual authentication of PEC/EC detection results, being conducive to increasing the assay reliability and accuracy. Such the dual-mode sensor has great potential for detecting environmental pollutants due to its improved selectivity and mutual authentication of results.
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