Bisphenol A Analogues Induce Neuroendocrine Disruption via Gut-Brain Regulation in Zebrafish
Xiyan Mu1, Zaiteng Liu1, Xiaoyu Zhao1
1Institute of Quality Standard and Testing Technology for Agro-Products, Chinese Academy of Agricultural Sciences, Beijing 100081, China.
Environmental Science & Technology
|January 2, 2024
Summary
Bisphenol G (BPG) and BPAF disrupt the gut-brain axis, impacting neuroendocrine function and behavior. These endocrine-disrupting chemicals affect neurotransmitter levels and gut-brain signaling pathways differently.
Area of Science:
- Environmental toxicology
- Neuroendocrinology
- Gut-brain axis research
Background:
- Epidemiological studies link endocrine-disrupting chemicals (EDCs) like bisphenol A (BPA) to neuroendocrine dysfunction.
- The precise mechanisms, especially concerning gut-brain regulation, remain unclear.
Purpose of the Study:
- To investigate the neuroendocrine and behavioral effects of BPA and its analogues (BPG, BPAF) in zebrafish.
- To elucidate the underlying mechanisms of bisphenol-induced gut-brain axis disruption.
Main Methods:
- Zebrafish embryos were exposed to varying concentrations of BPA, BPG, and BPAF.
- Neurotransmitter levels, enteroendocrine cell distribution, vagal neural development, and gene expression (scRNA-Seq) were analyzed.
- Immunofluorescence and immune staining were employed.
Main Results:
- BPG showed the most significant behavioral impact and neurotransmitter inhibition, followed by BPAF and BPA.
- BPG and BPAF altered enteroendocrine cell distribution, correlating with reduced neurotransmitter levels and activity.
- BPAF impaired vagal neural development, while BPG induced inflammatory responses in intestinal cells via TNFα-trypsin-EEC signaling.
Conclusions:
- BPG and BPAF disrupt the neuroendocrine system and gut-brain axis through distinct mechanisms.
- These findings offer new insights into how bisphenols mediate neuroendocrine disruption.
Related Concept Videos
Neural Regulation
Digestion begins with a cephalic phase that prepares the digestive system to receive food. When our brain processes visual or olfactory information about food, it triggers impulses in the cranial nerves innervating the salivary glands and stomach to prepare for food.
Hormonal Regulation
Hormones regulate a significant portion of digestion through activation of the neuroendocrine system. The neuroendocrine system of digestion contains many different hormones all with multiple functions that are both, directly and indirectly, involved in digestion.
Drugs Affecting GI Tract Motility: Dopamine Receptor Antagonists
Prokinetic agents are specialized medications that stimulate gastrointestinal (GI) motility, promoting food movement through the GI tract. Dopamine, an inhibitory neurotransmitter, plays a significant role in this process, reducing GI motility and indirectly controlling the speed of digestion. Dopamine receptor antagonists, such as metoclopramide and domperidone, offer a unique advantage as prokinetic agents. By blocking the dopamine receptors, these drugs increase GI motility, improving food...
Drugs Affecting GI Tract Motility: Serotonin Receptor Agonists
Serotonin, a crucial neurotransmitter synthesized by enterochromaffin cells, plays a cardinal role in regulating gastrointestinal (GI) motility. With over 90% of the body's total serotonin in the GI tract, its influence on digestive processes is profound. Serotonin is swiftly released upon various stimuli, such as food boluses or certain drugs, triggering intrinsic sensory neurons in the myenteric plexus and extrinsic vagal and spinal sensory neurons. This leads to the activation of the...
Regulation of Food Intake
Short-term regulation of food intake primarily involves neural signals from the gastrointestinal (GI) tract, blood nutrient levels, and GI tract hormones. Communication between the gut and brain via vagal nerve fibers plays a significant role in evaluating the contents of the gut. Clinical studies have shown that protein ingestion produces a more prolonged response in these nerve fibers compared to an equivalent amount of glucose. Additionally, the activation of stretch receptors caused by GI...
Gut-Brain Axis
The gut–brain axis is a bidirectional communication system that connects the gastrointestinal tract and the brain. This interaction is mediated through multiple pathways, including the vagus nerve, hormonal signals, immune responses, and chemical messengers produced by gut microbes.Microbial Contributions to Brain FunctionGut microbiota contributes significantly to brain function by producing neuroactive compounds. These include neuroactive compounds that influence neurotransmitters such as...


