| A novel class of organophosphate ester flame retardants called tris(1,3-dichloro-2-propyl)phosphate(TDCPP)has found widespread application in industrial materials.It has been extensively found in a variety of environmental mediums and organisms.Particularly representative neurotoxicity research,which has become a hot scientific topic in ecotoxicology,environment,and health.It is of significant concern regarding its effects on environmental and ecological harm and underlying biotoxicity mechanisms.The HP-m PFC circuit is composed of several direct and indirect fiber projections between the medial prefrontal cortex(m PFC)and the hippocampus(HP),two significant regions of the brain involved in learning,memory,and emotional control.Higher brain functions like learning,memory,emotion,and cognition have an immediate connection to it.The neuronal underpinnings of the aforementioned higher brain functions,known as synaptic plasticity,can exhibit changes in both their structural and functional flexibility.However,the majority of recent studies focused on in vitro cell culture and fish.Environmental toxicology in animals in vivo and multi-level combined investigation of toxicity processes are not well covered in the literature.A deeper and more thorough comprehension of the operations of the entire nervous system can be achieved by combining the HP-m PFC circuit with behavioral technological tools describing higher brain functions.Based on this,in order to elucidate the neurotoxic effects and characteristics of mice triggered by subchronic exposure to TDCPP,this study used male ICR mice as the research subject and combined behavior characterization analysis.By using electrophysiology,cell biology,and molecular biology techniques,the synaptic involved in the entire circuit was investigated as a means to clarify the neural mechanism of TDCPP toxic effects.The synaptic plasticity of the HP-m PFC circuit was applied as an indicator(including the number and structure of synapses,expression of synapticrelated proteins,changes in synaptic ultrastructure,etc.).Here are the following results:1)Behavioral research has shown that mice’s spontaneous activity behavior decreased in all experimental groups as the TDCPP exposure dose increased.For instance,in each experimental group,the number of cross squares showing the ability to move was dramatically decreased.In the medium and high concentration groups,there were instances of considerably less upright times that indicated their active exploration consciousness was reduced.In addition,the study discovered that mice in each concentration group showed significantly less novel object exploration and slightly lower recognition indexes when compared with the control group.The results demonstrated that TDCPP decreased mice’s emotional and cognitive levels while interfering with their capacity for memory and learning.2)Further mechanism research revealed that TDCPP could have an impact on the synaptic plasticity of the mice’s HP-m PFC circuit.TDCPP altered the density of the circuit’s dendritic spines,decreased the number of synapses and the thickness of postsynaptic density,and destroyed the two brain areas’ normal mitochondria structure.3)The research additionally showed that TDCPP can alter the electrical activity of medial prefrontal pyramidal neurons as well as increase the mean frequency of hippocampal pyramidal neurons in mice and improve the regularity of neuronal spike activities.It changed the synaptic functional plasticity in both the mice HP and m PFC as it decreased the amount of acetylcholine(ACh)present and raised the activity of acetylcholinesterase(ACh E).Conclusions: The present research’s preliminary findings support the hypothesis that subchronic exposure to TDCPP can impair mice’s capacity for learning and memory as well as their level of cognitive and affective expression,primarily by influencing the structural and functional plasticity of synapses in the HP-m PFC circuit. |
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