- About 32 million people globally have Alzheimer’s disease.
- People with Alzheimer’s disease experience both cognitive and non-cognitive symptoms.
- Researchers from the University of North Carolina at Chapel Hill were able to generate new neurons in the brain and stimulate them using deep brain stimulation via a mouse model.
- This process helped restore both cognitive and non-cognitive functions in a mouse model of Alzheimer’s disease.
An estimated 32 million people around the world have Alzheimer’s disease — a type of dementia for which there is currently no cure.
People with Alzheimer’s disease experience cognitive function degeneration, affecting their memory and ability to concentrate. They also have non-cognitive issues, including depression and anxiety.
Researchers from the University of North Carolina at Chapel Hill discovered they are able to generate new neurons in the brain and stimulate them using deep brain stimulation. This process helped restore both cognitive and non-cognitive functions in a mouse model of Alzheimer’s disease.
The study was recently published in the journal Cell Stem Cell.
What is deep brain stimulation?
Deep brain stimulation is a surgical procedure where electrodes are placed in specific areas of the brain. The electrodes are connected by wires to a small device, similar to a pacemaker, that is placed under the skin in the chest area.
The electrodes create electrical pulses that override abnormal signals that could cause neurological issues.
There has also recently been a move toward developing less invasive methods for deep brain stimulation.
Deep brain stimulation is used to treat a number of diseases, including:
- Parkinson’s disease
- epilepsy
- essential tremor
- dystonia
- obsessive-compulsive disorder (OCD)
Previous research has looked at deep brain stimulation as a potential treatment for Alzheimer’s disease.
A study in 2022 found deep brain stimulation in the fornix area of the brain helped reduce symptoms in people with Alzheimer’s disease.
And results from a clinical trial in 2018 showed deep brain stimulation of the brain’s frontal lobes could help slow function-related cognitive decline.
Creating new neurons in brains with Alzheimer’s
According to Dr. Juan Song, associate professor in the Department of Pharmacology and Neuroscience Center at the University of North Carolina at Chapel Hill and senior author of this study, the idea for studying the effect of deep brain stimulation on Alzheimer’s came from past research.
“One of the research focuses in my lab is to dissect the neural circuits regulating the process of generating new neurons in the adult brain using rodent models,” Dr. Song explained to Medical News Today. “This process is referred (to) as “adult hippocampus neurogenesis (AHN). Over years of studies in this area, we identified multiple key neural circuits that play critical roles in regulating AHN.”
“Recently, we reported that stimulating a brain region called (the) Supramammilary nucleus (SuM) located in the hypothalamus effectively promotes AHN in healthy mice,” she continued. “In this current study, we aim to assess whether this strategy can be applied to Alzheimer’s brains with impaired AHN to restore this process using Alzheimer’s mouse models.”
For the first portion of the study, scientists used optogenetics to stimulate the SuM and enhance AHN in Alzheimer’s mice. This generated new neurons in the brains of the mice with Alzheimer’s.
“In adult human brains, the hippocampus generates new neurons (adult-born neurons, or ABNs) across age,” Dr. Song detailed. “ABNs help us maintain memories and regulate emotions. In people with Alzheimer’s disease, this process is impaired, along with memory decline, elevated anxiety, and depression.”
“One way to help Alzheimer’s patients achieve symptom relief could be to enhance the function of ABNs,” she continued. “In this study, we demonstrate that stimulating SuM effectively enhanced ABNs in the otherwise impaired Alzheimer’s brains using rodent models. After patterned stimulation of SuM, AD brains developed more ABNs with improved qualities.”
Neuron activation
Next, Dr. Song and her team used a noninvasive type of deep brain stimulation called chemogenetics to activate the new neurons.
“Chemogenetics involves the use of inert molecules to alter the activity of brain cells expressing designer’s receptors,” Dr. Song said. “In this study, we use chemogenetics to increase the activity of SuM-enhanced ABNs, which appears to be critical for their beneficial effects on both cognitive and noncognitive symptoms in AD mouse models.”
“Importantly, activation of these SuM-modified ABNs restored both cognitive and affective deficits in AD mouse models,” she added.
Alzheimer’s disease treatment potential
Dr. Song said these findings may help guide new therapeutic strategies potentially through deep brain stimulation of SuM followed by drug treatment to boost the activity of SuM-enhanced ABNs.
“It has been shown that antidepressant ketamine treatment can effectively boost (the) activity of ABNs in rodent models,” she added.
As for the next steps in this research, Dr. Song said they plan to take unbiased approaches, such as multi-omics, to identify the genes and pathways mediated by the activation of SuM-enhanced ABNs.
“Following this step, efforts will be made to identify drug targets that could mimic the beneficial effects mediated by activation of SuM-enhanced ABNs,” she continued. “Ultimately, the hope is to develop first-in-class, highly targeted therapies to treat Alzheimer’s and related dementia.”
Could this work to treat Alzheimer’s in humans?
Medical News Today also spoke with Dr. Jean-Philippe Langevin, neurosurgeon and director of the Restorative Neurosurgery and Deep Brain Stimulation Program for Pacific Neuroscience Institute at Providence Saint John’s Health Center in Santa Monica, CA, who called this study “promising.”
“This study shows that they were not only able to regenerate neurons, but that those neurons that were regenerated were actually useful to carry the function that they need to do for memory, and also for emotional well-being,” he explained. “It’s two different things — you can regenerate new cells, but if they’re not functional, they’re not accomplishing any function inside the brain, they’re not properly connected, then you have no benefit.”
“So in this study, they were able to show that not only do you regenerate new cells, but that those cells were functional. And finally, that led to a clinical improvement for the (mice),” Dr. Langevin added. “The next step here that would help bridge the findings into humans would be if they were able to replicate similar findings by using a pharmacological agent — like if they had a drug that could target the same pathways — then that could be directly applied into clinical trials.”
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