Chemotherapy is the most commonly available form of cancer treatment, but its serious side effects are well-known. New research investigates the mechanism behind the cognitive impairment often associated with chemotherapy and offers new options for treating these adverse effects on the brain.
As many as 1 in 3 patients with cancer who undergo chemotherapy experience cognitive impairment as a result of the treatment. The cognitive dysfunction associated with chemotherapy is commonly referred to as "chemo brain."
The symptoms of chemo brain include difficulty remembering things, trouble concentrating and processing information, and overall confusion. A survey of cancer survivors has shown that this population are 40 percent more likely to report cognitive issues compared with their cancer-free counterparts.
At the most recent national meeting of the American Chemical Society, University of Kansas researcher and associate professor of chemistry, Michael Johnson, presented scientific studies suggesting a potential new treatment for chemotherapy-associated cognitive impairment.
"[Chemo brain is] something doctors learned about because patients were complaining," Johnson says. "Symptoms include visual and verbal memory loss - so if you have a conversation with somebody, you may have difficulty recalling it. You might have attention deficit, so if you are trying to do taxes, it might be difficult to focus. It also can result in a decline in processing speed, so it may be more difficult to think on your toes. You may have trouble remembering words."
The new findings presented by Johnson examine the brain chemistry behind this cognitive dysfunction, using rodent models. The studies also suggest new ways of treating the symptoms of chemo brain.
'KU-32' drug may prevent chemo brain
One such study referenced by Johnson - conducted by him in collaboration with David Jarmolowicz of the Department of Applied Behavioral Science at the University of Kansas, and colleagues - shows that a common chemotherapy drug called 5-Fluorouracil damages the integrity of myelin, the protective layer made of fats and proteins that forms around the brain cells.
This myelin damage corresponds to neurodegenerative deficits in the hippocampus - a brain area key to learning and memory - as well as dysfunctions in the cells' mitochondria, which are the so-called powerhouses of the cells, where the nutrients are transformed into energy.
Additionally, the study - published in the journal Behavioural Brain Research - shows that chemotherapy increases levels of hydrogen peroxide in the brain and that a chemical compound called KU-32 can counter the negative effects of this excessive substance. The research shows that KU-32 can stop the chemotherapy-induced cognitive decline in rats.
Michael Johnson explains the findings:
"In our preliminary results, we found that hydrogen peroxide temporarily increases in the brains of chemotherapy-treated rats. Because hydrogen peroxide is a reactive oxygen species and potentially damaging, it may have an effect on cognitive function. Additionally, we may have a therapy that can serve as a preventative in order to treat it. We found that KU-32 prevents cognitive impairment, and our preliminary neurochemical data suggest that it may prevent increases in hydrogen peroxide production."
Chemotherapy affects dopamine and serotonin
These results build on previous research carried out by Johnson and his colleagues. A recently published paper in the journal ACS Chemical Neuroscience examines the adverse effects of chemotherapy on the neurotransmitters dopamine and serotonin.
Dopamine is a major neurotransmitter that plays a key role in learning, memory, and other cognitive skills. Serotonin is largely associated with emotional states, as it helps to control mood and sleep quality, among other things.
"Dopamine is found in many regions of the brain but is particularly abundant in the striatum," Johnson says. "The striatum receives inputs from other parts of the brain, such as the cortex, and filters out the unwanted inputs while amplifying the wanted inputs, which are translated into actions. Dopamine is a key player in how the striatum responds. We felt that alterations in dopamine release due to chemo could potentially play a role in cognitive impairment."
Their study revealed that treatment with the common chemotherapy compound carboplatin impaired dopamine and serotonin release in the rats' brains. The rats treated with the drug released 42 percent less dopamine and 55 percent less serotonin than the rats that had not received the treatment.
"Serotonin is implicated in depression and cognitive function," Johnson explains. "We wanted to measure serotonin to see if this was a global effect. It turns out that serotonin is impacted as well, so it is likely that chemotherapy agents act on neurotransmitter systems other than dopamine as well and also play an important role."
Johnson notes that these findings may open up new avenues for treating chemo brain symptoms, as well as benefit research into other diseases.
"These are the first studies to our knowledge that look at what happens to neurotransmitter release events as a result of these chemotherapeutic agents. It hopefully will open up some options for treatments down the road [...] Certainly, it might be important for researchers interested in developing therapies for chemo brain as well as other disorders that might impact cognitive function."
Dr. Michael Johnson