The downregulation of TREM2 exacerbates toxicity of development and neurobehavior induced by aluminum chloride and nano-alumina in adult zebrafish.

To investigate the difference in the development and neurobehavior between aluminum chloride (AlCl) and nano-alumina (AlNPs) in adult zebrafish and the role of triggering receptor expressed on myeloid cells (TREM2) in this process. Zebrafish embryos were randomly administered with control, negative control, TREM2 knockdown, AlCl, TREM2 knockdown + AlCl, AlNPs, and TREM2 knockdown + AlNPs, wherein AlCl and AlNPs were 50 mg/L and TREM2 knockdown was achieved by microinjecting lentiviral-containing TREM2 inhibitors into the yolk sac. We assessed development, neurobehavior, histopathology, ultrastructural structure, neurotransmitters (AChE, DA), SOD, genes of TREM2 and neurodevelopment (α1-tubulin, syn2a, mbp), and AD-related proteins and genes. AlCl significantly lowered the malformation rate than AlNPs, and further increased rates of malformation and mortality following TREM2 knockdown. The locomotor ability, learning and memory were similar between AlCl and AlNPs. TREM2 deficiency further exacerbated their impairment in panic reflex, microglia decrease, and nerve fibers thickening and tangling. AlCl, rather than AlNPs, significantly elevated AChE activity and p-tau content while decreasing TREM2 and syn2a levels than the control. TREM2 loss further aggravated impairment in the AChE and SOD activity, and psen1 and p-tau levels. Therefore, AlCl induces greater developmental toxicity but equivalent neurobehavior toxicity than AlNPs, while their toxicity was intensified by TREM2 deficiency.