PNAS: Tracing brain circuits to chemotherapy 'side effect clusters'

Severe and persistent disability often compromises the life-saving benefits of cancer treatment

A new study by researchers at the Georgia Institute of Technology in the lab of Timothy C.

New findings "Neural circuit mechanisms of sensorimotor disability in cancer treatment" published in the Proceedings of the National Academy of Sciences (PNAS) may impact the development of effective treatments that have not yet been used in cancer treatment to restore a patient's normal ability to receive and process sensory input

Nervous system effects

"Chemotherapy undoubtedly negatively affects the peripheral nervous system, which is often thought to be the culprit in neurological disturbances during cancer treatment," Hausley shared

This is achieved through synaptic communication between neurons

"These disabilities are not clinically alleviated and are also unexplained empirically because studies have focused on peripheral degeneration of sensory neurons and underestimated the possible involvement of neural processes in the central nervous system," the team explained in their study.

sensorimotor disorder

The team noted that cancer survivors "rank sensorimotor impairment as one of the most distressing long-term consequences of chemotherapy

The team addressed this omission "by using a combination of electrophysiology, behavior, and modeling to study the functioning of spinal sensorimotor circuits in vivo," Cope said, in "Chronic Oxaliplatin (Chemotherapy)-Induced Neuropathy: cOIN" ” in a rodent model

Key sequential events are studied in the encoding of "proprioceptive" information (think kinesthetic: the body's ability to perceive its own position, movement, and action) and its circuitry to convert synaptic potentials generated by motor neurons

In 'coin' rats, the team noticed that multiple proprioceptive neurons exhibited defective firing, reducing accurate sensory representations of the muscle's mechanical response to stretching, he added, "due to defective mechanisms within the spinal cord.

Joint expression, independent defect

"The combination of these sequential, peripheral and central deficits leads to a functional breakdown of the sensorimotor circuit, which produces significant errors in predicting proprioceptive-guided motor behavior," Cope and Housley report

"These findings have broad implications for the scientific field and the clinical management of the neurological consequences of cancer treatment," Housley said

Houseley also said that the ability to monitor nerve function at different sites during treatment "will provide us with a biomarker to optimize therapy