Aging brains are often misunderstood. Older adults go through changes neurologically, but it does not mean intelligence is lost. Now, University researchers are examining how surgery and aging can specifically affect older brains and how aging brains could recover.
Uwe Rudolph, professor in Veterinary Medicine, and postdoctoral researcher Rajasekar Nagarajan, decided to investigate postoperative impairment and age-related memory decline. Rudolph’s lab published two recent research articles showing these deficits could be improved with medications, shown through experiments with mice.
Previous literature has established that older adults are more susceptible to inflammation in the brain after surgery due to the aging brain. Surgery leads to immune system activation, which can inflame the brain.
“In surgery, it activates the peripheral immune cells, like neutrophils and monocytes,” Nagarajan said. “They go to the brain and damage the blood-brain barrier … making more inflammation, that leads to memory impairment.”
In their first paper, the researchers examined post-surgical cognitive impairment in older adults. Studies have shown that older adults over the age of 60 may lose function in their brains after surgery. By using a common anesthetic called propofol, they were able to see if the agent could help with cognition post-surgery. To successfully test this theory, the team performed surgery on older mice and ran tests.
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“We have various animal behavioral tests in the lab,” Nagarajan said. “First, we test to see if there is any change in the locomotor activity. Then, we did a maze test … testing memory deficit.”
After performing these tests, the team was able to find that, by administering propofol to the mice before their surgeries, the mice were able to succeed in their performance within the cognitive tasks given.
Specifically, their findings led them to examine GABA, a neurotransmitter — a chemical signaling molecule in the brain. GABA is located in the hippocampus; these molecules are essential regulators for cognitive processes and memory. They work by binding to a receptor to exert some particular effect.
Mice that were given propofol had an increase of receptors for GABA, which ultimately led to less visible cognitive decline.
In their second paper, the focus was on age-related memory impairment. Studies found that insulin nasal spray improved memory in Alzheimer’s disease models, so the pair tested to see if the spray improved age-related memory impairment.
“The older brains and the younger brains look different,” said Hye Soo Lee, a postdoctoral research associate in a separate research group — the Human Factors and Aging Laboratory. “(Aging) affects intelligence, not that (older adults) lose their intelligence.”
Rudolph’s lab used a mouse model where they mimicked aging within the mice — naming them “pseudo-aged mice.” They used a control group to see if the nasal spray actually improved the mice’s tasks. The nasal spray aided in tasks related to memory, and the tests showed that the spray actually regulated neural inflammation for the pseudo-aged mice.
Their findings inch closer to working with human aging brains. The researchers hope to continue their investigation to understand the details and to see if the findings apply to other drugs.
“We found a variety of biochemical parameters that change in aging that can be normalized by insulin,” Rudolph said. “We want to see if the GABA receptors are redistributed in cells and if that is present with drugs that can be used in general medical settings, like benzodiazepines.”
