Tiny Brain Bubbles: Uncovering Complete Code

These small extracellular vesicles (sEVs) are the focus of this study. Researchers have discovered that these tiny biological bubbles in the brain are important. rnrnThe body’s cells create small, bubble-like structures called extracellular vesicles (EVs) to transport various proteins, lipids, and byproducts of cellular processes, as well as RNA nucleic acid codes used by recipient cells to produce new proteins. Scientists are particularly interested in EVs produced by the brain because they can transmit both normal and flawed instructions for misfolded proteins, which accumulate in the brain during neurodegenerative diseases like Alzheimer’s. If EVs are to contribute to the accumulation of these abnormal proteins, they must contain the necessary instructions.The study discovered that previous research had suggested that messenger RNA (mRNA) carrying plans for proteins were cut into too many shorter fragments to allow recipient cells to change their construction patterns. However, the new study found the opposite to be true, identifying more than 10,000 full-length mRNAs using a newer DNA sequencing technique called PacBio long-read sequencing. Chun, a professor at the Center for Genetic Disorders and Aging Research at Sanford Burnham Prebys, stated, “We found quite the opposite to be true in our study.” The team isolated sEVs from the.In a study involving the prefrontal cortex of 12 postmortem brain samples from Alzheimer’s patients and 12 from donors without neurological diseases, it was discovered that almost 80% of the identified mRNAs were full-length. This means that these mRNAs can be transcribed into viable proteins by recipient cells. Additionally, the study looked at vesicles isolated from mouse cells and found similar averages of full-length transcripts in three different brain cell types, ranging from 78% to 86%. This suggests that the findings in human samples were corroborated by the results from mouse cells.

The researchers examined the length of mRNAs in brain sEVs and compared the gene sequence reflected in the sEV mRNA transcriptome. In Alzheimer’s disease samples, they found that 700 genes showed increased expression, while nearly 1500 genes had reduced activity.

They concluded that the 700 upregulated genes are linked to inflammation and immune system activation, which aligns with the known patterns of brain inflammation in neurodegenerative diseases like Alzheimer’s. The scientists also identified the association between sEVs, microglia and neurons.

Numerous genes linked to Alzheimer’s disease in previous genome-wide association studies were also found in Alzheimer’s disease sEVs.

“The alterations in gene expression found in these vesicles indicate an inflammatory signature that could provide insight into the disease processes taking place in the brain as Alzheimer’s disease advances,” Chun explains.

Following this research, Chun and his team will further explore how cells package sEVs and how the mRNA enclosed within them leads to functional changes in other brain cells affected by Alzheimer’s disease. A better understanding of sEVs and their mRNA contents could facilitate the identification of biomarkers.The researchers hope to use sEVs for improved early detection of Alzheimer’s and other neurological conditions, as well as to uncover new disease mechanisms for potential therapeutic targets. Chun also suggests the possibility of using sEVs as a targeted delivery system for future brain therapies. Other authors of the study include Linnea S. Ransom, Christine S. Liu, Emily Dunsmore, Carter R. Palmer, Juliet Nicodemus, Derya Ziomek, and Nyssa Williams, all at Sanford Burnham Prebys.The study received funding from the National Institute on Aging (R01AG065541 and R01AG071465), National Institute of General Medical Sciences (T32GM007752), and Rotary International.