Developmental exposure to environmental levels of cadmium induces neurotoxicity and activates microglia in zebrafish larvae: From the perspectives of neurobehavior and neuroimaging

Wnt/β-Catenin Signaling Pathway Is Strongly Implicated in Cadmium-Induced Developmental Neurotoxicity and Neuroinflammation: Clues from Zebrafish Neurobehavior and In Vivo Neuroimaging

“…Waldo Cerpa et al showed that this pathway also functions in synaptic transmission and activity-dependent synaptic plasticity [ 65 ]. In addition, our previous studies showed that Cd 2+ impairs the early neurodevelopment of zebrafish by inducing cell cycle arrest and apoptosis [ 47 ]; therefore, naturally, we speculated that the damaging effects of Cd 2+ to the CNS development of zebrafish might be closely related to the Wnt/β-catenin signaling pathway.…”

“…Because of its conserved relationship with human beings in CNS structure and function, zebrafish is currently one of the most valuable model systems used to study neurotoxicity induced by various environmental pollutants [ 56 ]. Recently, taking full advantages of zebrafish in live neuroimaging and neurobehavioral tracking, we performed in-depth studies of the effects of environmental levels of Cd 2+ on the early development, structure, and function of the CNS [ 47 ], and on this basis, we explored the molecular mechanisms of Cd 2+ -induced neurotoxicity. Briefly, in this study, we focused on the implications of the Wnt/β-catenin signaling pathway, and revealed that (1) Cd 2+ exposure significantly affected the expression of key factors in the zebrafish Wnt/β-catenin signaling pathway; (2) pharmacological activation of the Wnt/β-catenin signaling pathway significantly repressed the Cd 2+ -induced cell cycle arrest and apoptosis, thereby attenuating the inhibitory effects of Cd 2+ on early development, behavior, and activity, as well as the neurodevelopment of zebrafish larvae; (3) activation and proliferation of microglia, as well as the altered expression profiles of genes associated with neuroimmune homeostasis triggered by Cd 2+ exposure, could also be significantly alleviated by the activation of the Wnt/β-catenin signaling pathway.…”

“…The morphological characteristics of zebrafish embryos/larvae were recorded under the stereomicroscope at different developmental stages ranging from 2 hpf to 144 hpf. Briefly, mortality as well as other parameters including hatchability, body length, cardiac rate, and malformation of embryos/larvae were recorded as previously reported [ 47 ]. In addition, the early developmental process (from 2.5 hpf to 24 hpf) of zebrafish embryos was continuously video recorded and then analyzed through the high-throughput dynamic imaging system (DynaPlant, YPHbio, Beijing, China) in the Experiment Center of the School of Life Sciences, according to the user’s manual [ 80 ].…”

“…One of our recent studies showed that early development of zebrafish was delayed, and neurobehavioral patterns including spontaneous activity and reactivity to different environmental signals were significantly disturbed during developmental Cd 2+ exposure. Importantly, we revealed associations between Cd toxicity and neurodevelopmental disorders as well as microglia-mediated neuroinflammation [ 47 ]. However, the underlying neurotoxic mechanisms remain largely unclear.…”

Fish Behavior as a Neural Proxy to Reveal Physiological States

“…Silver impairs social preferences, social recognition, learning, and memory in adult zebrafish ( Fu et al, 2021 ). Cadmium induces CNS impairment and neuroinflammation and impairs social behaviors, escape behaviors, and predator responses in rainbow trout, sea bass, and zebrafish ( Sloman et al, 2003 ; Blechinger et al, 2007 ; Faucher et al, 2008 ; Xu et al, 2022 ). Lead-exposed zebrafish exhibited decreased learning and altered color preferences ( Bault et al, 2015 ; Xu et al, 2016 ).…”