Like a great orchestra, your brain relies on the perfect coordination of many elements to function properly. And if one of those elements is out of sync, it affects the entire ensemble. In Alzheimer’s disease, for instance, damage to specific neurons can alter brainwave rhythms and cause a loss of cognitive functions.
One type of neuron, called inhibitory interneuron, is particularly important for managing brain rhythms. It’s also the research focus of a laboratory led by Jorge Palop, PhD, assistant investigator at the Gladstone Institutes. In a study published in Neuron, Palop and his collaborators uncovered the therapeutic benefits of genetically improving these interneurons and transplanting them into the brain of a mouse model of Alzheimer’s disease.
Interneurons control complex networks between neurons, allowing them to send signals to one another in a harmonized way. You can think of inhibitory interneurons as orchestra conductors. They create rhythms in the brain to instruct the players—excitatory neurons—when to play and when to stop. An imbalance between these two types of neurons creates disharmony and is seen in multiple neurological and psychiatric disorders, including Alzheimer’s disease, epilepsy, schizophrenia, and autism.
A Brain without a Conductor
Palop’s previous studies showed that, in mouse models of Alzheimer’s, the inhibitory interneurons do not work properly. So, the rhythms that organize the excitatory cells are disturbed and fail to function harmoniously, causing an imbalance in brain networks. This, in turn, affects memory formation and can lead to epileptic activity, which is often observed in patients with Alzheimer’s disease.
His team found a way to reengineer inhibitory interneurons to improve their function. They showed that these enhanced interneurons, when transplanted into the abnormal brain of Alzheimer mice, can properly control the activity of excitatory cells and restore brain rhythms.
“We took advantage of the fact that transplanted interneurons can integrate remarkably well into new brain tissues, and that each interneuron can control thousands of excitatory neurons,” said Palop, who is also an assistant professor of neurology at the University of California, San Francisco. “These properties make interneurons a promising therapeutic target for cognitive disorders associated with brain rhythm abnormalities and epileptic activity.”
First, the scientists had to overcome a significant challenge. When they transplanted regular interneurons, they saw no beneficial effects, presumably because Alzheimer’s disease creates a toxic environment in the brain.
The researchers then genetically boosted the activity of inhibitory interneurons by adding a protein called Nav1.1. They discovered that the interneurons with enhanced function were able to overcome the toxic disease environment and restore brain function.
“These optimized neurons are like master conductors,” said Palop. “Even with a declining orchestra, they can restore the rhythms and harmony needed for cognitive functions.”
Conductors Engineered for Alzheimer’s Disease
The findings could eventually lead to the development of new treatment options for patients with Alzheimer’s disease.
“Besides the applications this cell engineering and transplantation approach may find in regenerative medicine, our findings support the broader concept that enhancing the function of interneurons can counteract key aspects of Alzheimer’s disease,” said Lennart Mucke, MD, director of the Gladstone Institute of Neurological Disease.
In addition to examining if the cell therapy could be translated from mice to humans, Palop and his team are working to identify potential drugs as an alternative way to enhance the function of inhibitory interneurons.
The Latest on: Alzheimer’s Disease
via Google News
The Latest on: Alzheimer’s Disease
- Could new discovery play a role in diagnosing Alzheimer's earlier?on February 27, 2020 at 9:57 am
"We've detected an early sign of the disease in a DNA modification, or epigenetic marker, that was previously overlooked, and that could even provide a starting point for developing new therapies, as ...
- Berwyn biotech firm taking on Alzheimer’s disease receives $1.7M NIH granton February 27, 2020 at 8:13 am
Berwyn biotech firms gets $1.7M NIH grant to support development of a new drug candidate for the treatment of Alzheimer's and Parkinson's diseases.
- Blue Cross Plans Say Alzheimer’s Has Tripled Among Adults Ages 30 To 64on February 27, 2020 at 3:02 am
Early-onset dementia and Alzheimer’s disease jumped 200% among commercially insured Americans between the ages of 30 and 64 over a recent five-year period, a new analysis of Blue Cross and Blue Shield ...
- Delivering Crocetin across the Blood-Brain Barrier by Using γ-Cyclodextrin to Treat Alzheimer’s Diseaseon February 27, 2020 at 2:32 am
Crocetin (CRT) has shown various neuroprotective effects such as antioxidant activities and the inhibition of amyloid β fibril formation, and thus is a potential therapeutic candidate for Alzheimer’s ...
- Widowhood accelerates cognitive decline among those at risk for Alzheimer's diseaseon February 27, 2020 at 12:21 am
Investigators from Brigham and Women's Hospital and Massachusetts General Hospital analyzed older, cognitively normal Americans enrolled in the Harvard Aging Brain Study whose marital status and brain ...
- Scientists find new way to save neurons in Alzheimer’s diseaseon February 26, 2020 at 8:34 am
Neurons die earlier than experts previously thought in Alzheimer’s disease, and stopping the process could prevent the disease from ever developing, finds a new study from Tokyo Medical and Dental ...
- Prediction of Alzheimer’s disease using blood gene expression dataon February 26, 2020 at 2:36 am
Identification of AD (Alzheimer’s disease)-related genes obtained from blood samples is crucial for early AD diagnosis. We used three public datasets, ADNI, AddNeuroMed1 (ANM1), and ANM2, for this ...
- Is Alzheimer’s Disease Actually a Sleep Disorder?on February 25, 2020 at 10:54 am
Alzheimer’s disease is a form of dementia that occurs when there is a buildup of damaging toxic plaque in the brain. This amyloid plaque is essentially poison to our brain cells. Wherever amyloids ...
- Lifestyle Guru B. Smith Dies at 70 From Early Onset-Alzheimer's Disease—Here's What That Meanson February 24, 2020 at 3:10 pm
"It is with great sadness that my daughter Dana and I announce the passing of my wife, Barbara Elaine Smith," her husband, Dan Gasby, said in a statement shared to Facebook. "B. died peacefully ...
via Bing News