Study maps how brain stimulation alters genes in living human tissue

Researchers have for the first time mapped how deep brain stimulation alters gene expression across individual cell types in living human brain tissue, a step that could open new avenues for treating cognitive decline.

From Patient Tissue to Molecular Map

In a study published Wednesday in Nature, scientists from UCLA Health and the University of Texas Southwestern Medical Center used donated human temporal cortex tissue — kept alive in a lab for several days after surgical removal — to apply electrical stimulation patterns resembling deep brain stimulation and then track the molecular consequences at single-cell resolution.uclahealth+1

Deep brain stimulation, which delivers electrical impulses through implanted devices, is already used to treat Parkinson's disease and obsessive-compulsive disorder. But its effects on the different cell types within the human brain, and the genes those cells activate in response, have until now been studied only in animal or lab-grown tissues.neurosciencenews+1

The team developed what they describe as an "ex vivo platform" that integrates microelectrode array stimulation with simultaneous neural recording and single-nucleus genomics. After stimulation, brain cells became more synchronized in how they fired — a pattern associated with memory formation. The researchers then isolated individual cell nuclei and cataloged each cell type's genetic activity.genengnews+1

Astrocytes Join the Response

Among the study's more notable findings is that non-neuronal support cells called astrocytes activated their own distinct genetic programs during stimulation, independent of neuronal responses. Neurons and astrocytes each switched on separate sets of genes, suggesting that deep brain stimulation engages broad glial-neuronal networks rather than simply triggering electrical firing in neurons alone.genengnews+1

The researchers also validated their laboratory findings against tissue from patients who had undergone clinical deep brain stimulation before surgery, confirming that similar gene expression patterns occur inside the living brain.medicalxpress+1

Toward Precision Therapies

"By understanding exactly which genes turn on in which cells during stimulation, we can start to design more precise approaches to deep brain stimulation and potentially augment this clinical strategy with pharmacological therapies to help slow cognitive decline," said senior author Genevieve Konopka, chair of the Department of Neurobiology at UCLA Health.uclahealth+1

The researchers acknowledged that further work is needed to understand the effects of long-term stimulation, how activated cells influence their neighbors, and how deeper brain regions — harder to obtain from living donors — respond at the molecular level.medicalxpress