The common therapeutic drug paclitaxel (PTX) causes “chemo-brain,” a phenomenon seen in cancer patients during and after chemotherapeutic treatment. It is characterized by mental cloudiness, including confusion, memory problems, and increased anxiety. However, the neuronal and synaptic mechanism underlying the pathophysiological effects of PTX in the central nervous system (CNS) is not yet well-defined. We anticipated PTX to negatively impact the health and morphological structure of neurites and synapses. Our investigation involved culture of mouse cortical neurons in physiologically relevant low (10nM) and high (1µM) concentrations of PTX and examined its effects on viability with live/dead assay, neurite outgrowth with phase contrast imaging, and formation of chemical and electrical synapses with immunocytochemistry. We found that PTX significantly reduced neuronal viability in high, but not low, concentrations. Similarly, it significantly reduced development of neurites, which are critical for signal transmission. Specifically, both 10nM and 1µM PTX significantly reduced the number of primary, secondary, and total neurites per neuron. 1µM PTX, but not 10nM PTX, also significantly reduced the average length of primary, secondary, and overall neurites. PTX appears to also affect protein expression of chemical and electrical synapse markers. Our results demonstrate that PTX negatively impacts all features we examined, including cell viability, neurite outgrowth, and both electrical and chemical synapses. Our study enhances the understanding of PTX’s neurotoxic effects on the CNS, and for the first time demonstrates an impact on electrical synapses.

Dr. Xu has been Julia’s PI for the past few years, while Julia has done research in her lab. Dr. Xu has been an incredibly positive influence on Julia’s years at SLU. She has taught Julia many skills, both applicable within the lab and outside of it. Dr. Xu brightens everyone’s day with her positivity, kindness, and infectious enthusiasm. She demonstrates and inspires in Julia a passion for research and curiosity. Julia will forever be thankful for Dr. Xu’s support, mentorship, kindness, wisdom, and friendship.