Berberine exposure triggers developmental effects on planarian regeneration

Abstract

The mechanisms of action underlying the pharmacological properties of the natural alkaloid berberine still need investigation. Planarian regeneration is instrumental in deciphering developmental responses following drug exposure. Here we report the effects of berberine on regeneration in the planarian Dugesia japonica. Our findings demonstrate that this compound perturbs the regenerative pattern. By real-time PCR screening for the effects of berberine exposure on gene expression, we identified alterations in the transcriptional profile of genes representative of different tissues, as well as of genes involved in extracellular matrix (ECM) remodeling. Although berberine does not influence cell proliferation/apoptosis, our experiments prove that this compound causes abnormal regeneration of the planarian visual system. Potential berberine-induced cytotoxic effects were noticed in the intestine. Although we were unable to detect abnormalities in other structures, our findings, sustained by RNAi-based investigations, support the possibility that berberine effects are critically linked to anomalous ECM remodeling in treated planarians.

Planarian brain regeneration as a model system for developmental neurotoxicology

“…While other groups have normalized by the area of the worm (Balestrini et al. ; Kustov et al. ), we found that normalizing by the square of the worm's width was the most accurate way to account for size variation (Hagstrom et al.…”

“…), and substances with unclear toxicity such as the natural alkaloid berberine (Balestrini et al. ) or silver nanoparticles (Kustov et al. ).…”

“…We and others have used high‐resolution light microscopy to quantify the rate of blastema growth during regeneration (Balestrini et al. ; Kustov et al. ; Hagstrom et al.…”

“…Because the blastema is unpigmented, it can easily be distinguished from the rest of the pigmented worm body, allowing for automated image analysis (Balestrini et al. ; Kustov et al. ; Hagstrom et al.…”

“…However, as with studies on adult worms, these behavioral tests have been limited in their throughput and range of behaviors tested, primarily relying on pLMV and phototaxis (Balestrini et al. ; Lowe et al. ; Stevens et al.…”