New Nasal Spray Therapy Shows Promise in Restoring Memory and Cognitive Function in Aged Brains

Researchers affiliated with Texas A&M University have published a study in the Journal of Extracellular Vesicles titled "Intranasal Human NSC-Derived EVs Therapy Can Restrain Inflammatory Microglial Transcriptome, and NLRP3 and cGAS-STING Signalling, in Aged Hippocampus." This report details the development of a novel nasal spray designed to suppress age-related brain inflammation and restore memory and cognitive functions.

The decline in memory and cognitive abilities associated with aging is deeply linked to chronic, low-grade inflammation in the hippocampus, the brain region responsible for memory. This inflammation is not a severe, fire-like event, but rather a smoldering ember, which contributes to forgetfulness and cognitive impairment.

To address this challenge, the current research aims to improve the condition through a new therapeutic approach that utilizes "extracellular vesicles" (EVs), which are extremely small capsules secreted by neural stem cells derived from human induced pluripotent stem cells (iPS cells). These EVs are being investigated as a means to halt age-related brain damage.

The research team administered this EVs therapy to middle-aged mice, equivalent to about 60 years old in humans (18 months old), by applying it nasally twice, similar to a nasal spray. They then evaluated the subsequent changes in the brain and cognitive functions of these mice.

Analysis of the hippocampus in mice that received the EVs showed a reduction in oxidative stress that damages cells, and the abnormal accumulation of microglia, the brain's immune cells, was suppressed. Furthermore, it was confirmed that genes responsible for maintaining the normal function of mitochondria, the energy source for cells, were activated, enhancing the brain's protective functions.

The key to the therapeutic effect lies in the microRNAs, active components abundant in EVs. It was revealed that these microRNAs block specific signaling pathways (such as the NLRP3 inflammasome and cGAS-STING pathways) that trigger inflammation in the brain, thereby suppressing inflammation at its root.

Additionally, gene expression analysis of individual cells revealed significant changes in the nature of microglia that had taken up the EVs. The activity of genes that induce inflammation decreased, while functions that enhance cellular energy production and repair tissues became more active. This indicates that the brain's immune cells switched from an inflammatory mode to a protective mode.

These improvements in the brain's internal environment have translated into actual performance enhancements. In behavioral tests measuring memory and cognitive functions, such as object recognition and the ability to detect changes in new environments, aged mice treated with the EVs therapy showed improved scores.