Impact of Copper Nanoparticles and Copper Ions on Transcripts Involved in Neural Repair Mechanisms in Rainbow Trout Olfactory Mucosa

Abstract

Olfactory mucosa is well-known for its lifelong ability for regeneration. Regeneration of neurons and regrowth of severed axons are the most common neural repair mechanisms in olfactory mucosa. Nonetheless, exposure to neurotoxic contaminants, such as copper nanoparticles (CuNPs) and copper ions (Cu 2+ ), may alter the reparative capacity of olfactory mucosa. Here, using RNA-sequencing, we investigated the molecular basis of neural repair mechanisms that were affected by CuNPs and Cu 2+ in rainbow trout olfactory mucosa. The transcript profile of olfactory mucosa suggested that regeneration of neurons was inhibited by CuNPs. Exposure to CuNPs reduced the transcript abundances of pro-inflammatory proteins which are required to initiate neuroregeneration. Moreover, the transcript of genes encoding regeneration promoters, including canonical Wnt/β-catenin signaling proteins and developmental transcription factors, were downregulated in the CuNP-treated fish. The mRNA levels of genes regulating axonal regrowth, including the growth-promoting signals secreted from olfactory ensheathing cells, were mainly increased in the CuNP treatment. However, the reduced transcript abundances of a few cell adhesion molecules and neural polarity genes may restrict axonogenesis in the CuNP-exposed olfactory mucosa. In the Cu 2+ -treated olfactory mucosa, both neural repair strategies were initiated at the transcript level. The stimulation of repair mechanisms can lead to the recovery of Cu 2+induced olfactory dysfunction. These results indicated CuNPs and Cu 2+ were differentially affected the neural repair mechanism in olfactory mucosa. Exposure to CuNP had greater effects on olfactory repair mechanisms relative to Cu 2+ and dysregulated the transcripts associated with stem cell proliferation and neural reconstitution.

A surge of cytosolic calcium dysregulates lysosomal function and impairs autophagy flux during cupric chloride–induced neuronal death

“…For example, Cu ions are required to activate MEK/ERK pathway and increased expression of various transcription factors ( 78 ). Cu 2+ and copper nanoparticles affect neuronal repair-gene transcription levels in olfactory mucosa ( 79 ). Cu ions bind classic metal-binding transcription factors and chaperones, including MTF1 and SP1, and regulate gene expression ( 80 ).…”

Zebrafish Insights into Nanomaterial Toxicity: A Focused Exploration on Metallic, Metal Oxide, Semiconductor, and Mixed-Metal Nanoparticles

“…Cu 2+ treatment initiated both neural repair strategies and led to recovery from olfactory dysfunction. Overall, CuNPs had a greater impact on olfactory repair mechanisms than Cu 2+ [74].…”