A simple nasal spray might sound modest, but in mice it did something researchers have been chasing for years. It reduced inflammation in the aging brain and restored lost memory function, according to a team at Texas A and M University.
The researchers say the treatment targets “neuroinflammaging”, small pockets of chronic stress in the aging brain that are linked to age-related cognitive decline and are thought to play a role in neurological disorders such as Alzheimer’s.
They compare neuroinflammaging to parts of an engine that are always running hot.
In the study, the spray targeted those hotspots using millions of microscopic biological bubbles called extracellular vesicles, or EVs. The EVs were produced from human stem cells and packed with proteins and genetic instructions.
The team tested the treatment in 18-month-old male and female mice, an age commonly treated as older adulthood in mouse studies and roughly comparable to humans in their late 50s to late 60s.
The mice received two intranasal doses spaced two weeks apart. The researchers said delivering the treatment through the nose may help the EVs reach the brain more directly without invasive surgical procedures, and reported that the vesicles were quickly absorbed.
After the two doses, the treated mice outperformed control mice on tasks measuring object recognition and spatial memory. Further biochemical analysis of the hippocampus suggested the treatment had the intended effect on brain inflammation.
The researchers focused on microglia, the brain’s immune cells, in the hippocampus, a region involved in memory and learning where significant neuroinflammation occurs.
Inside the EVs are microRNAs, tiny pieces of genetic code that regulate gene expression. The researchers said those microRNAs rewired brain cells to turn off or reduce some of the alarm signalling that drives neuroinflammaging.
In the aging mice, that shift meant microglia were able to reset to a more normal state, including the way mitochondria managed energy.
“MicroRNAs act like master regulators. They help modulate and regulate many gene and signaling pathways in the brain,” neuroscientist Madhu Leelavathi Narayana said.
“We are giving neurons their spark back by reducing oxidative stress and reactivating the brain’s mitochondria.”
The team said using healthy stem cells is an approach now being widely investigated for its therapeutic potential. They also said earlier work has established that stem cell byproducts such as EVs can do much of the beneficial work while being safer to transfer into the body.
The researchers believe similar results could be seen in people with further research and development.
“As we develop and scale this therapy, a simple, two-dose nasal spray could one day replace invasive, risky procedures or maybe even months of medication,” neuroscientist Ashok Shetty said.
“It’s universal. Treatment outcomes were consistent and similar across both sexes.”
The findings point to a possible new approach to reducing age-related neuroinflammation that can spark dementia. New dementia cases in the United States alone could hit a million a year by 2060, double the current level, according to the source text.
The report also noted that other animal studies have suggested related EV therapies may help recovery after stroke or brain injury.
Human trials will be needed to determine if the treatment can help conditions such as mild cognitive impairment, the researchers said.
Shetty said the work sits within broader efforts to support healthier aging with less biological wear and tear.
“Brain age-related diseases like dementia are a major health concern worldwide,” Shetty said.
“We’re aiming for successful brain aging: keeping people engaged, alert, and connected. Not just living longer, but living smarter and healthier.”
The research has been published in the Journal of Extracellular Vesicles.
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