JUL 27, 2016 6:31 AM PDT

PET Scan to Visualize Synaptic Density in the Living Brain

WRITTEN BY: Cassidy Reich
Synapses are the connections between neurons that allow them to communicate with each other. When synapses become compromised and can no longer effectively communicate, they are lost, and brain function suffers. Synaptic density would be a great measure for diagnosis and for tracking neuropathology in certain diseases, but there is currently no way to look at synaptic density in the living brain. Evaluating synaptic density requires brain tissue from autopsy or surgical resection. However, scientists have developed a new radioligand for PET (positron emission tomography) scans that is capable of measuring synaptic density in the living brain.

There are ~100 trillion synapses in the human brain.
This research was recently published in Science Translational Medicine and described PET studies with a new radioligand that were conducted in non-human primates, healthy human subjects, and epileptic patients with mesial temporal lobe sclerosis.

Usually when measuring synaptic density in brain tissue, researchers will use an antibody against synaptophysin, a protein that is present in every single presynaptic vesicle. However, there is currently no radioligand that can be used for PET that binds to synaptophysin. The company UCB does have an antiepileptic drug, levetiracetam, that targets another synaptic vesicle protein, SV2A. A derivative of this drug, [11C]UCB-J, is the radioligand that was tested in these studies and has been shown to specifically bind to SV2A. SV2A, just like synaptophysin, is present in every synapse.

When they tested [11C]UCB-J in non-human primates, they saw a signal in gray matter and none in white matter, which makes sense. Gray matter consists of the axons and dendrites of neurons, i.e. where the synapses are, and white matter is the cell bodies of those neurons. To investigate the quantitative nature of their tracer, the scientists also cross-validated PET signals with post-mortem brain tissue analysis of SV2A protein levels in several brain regions.

Following non-human primate studies, [11C]UCB-J was tested in healthy human subjects and was found to be effective and had favorable kinetics. The real test was to do a PET scan with [11C]UCB-J in epileptic patients with mesial temporal lobe sclerosis. In patients with this condition, there is loss of synapses in the hippocampus in one hemisphere and the atrophy is also visible on MRI. With this new tracer, the scientists were able to visualize the loss in synaptic density in the hippocampus on the affected side compared to the unaffected side, and were also able to correlate the synapse loss with degree of atrophy.  


This is a crazy advancement for neuroimaging because synapse loss is present in so many neurological conditions and is also one of the pathological events in Alzheimer’s disease (AD) that closely tracks with cognitive decline. When neurons die, they die, and there is no getting them back. But it might be possible to reverse damage to the synapses which is the step that precedes neuronal loss in AD. Which this kind of imaging, it will be possible to monitor the effect of early interventions in AD on synaptic density, a measure that correlates with cognitive decline more so than other biological markers.

I have barely scratched the surface, and if you are interested, I strongly suggest looking at the original article in Science Translational Medicine and also this great write-up on AlzForum.
About the Author
  • Cassidy is a curious person, and her curiosity has led her to pursue a PhD in Pharmacology at the New York University Sackler Institute of Biomedical Sciences. She likes to talk about science way too much, so now she's going to try writing about it.
You May Also Like
MAY 11, 2021
Immunology
Immune Cells Help Brain Tumors Spread, but We Can Stop Them
MAY 11, 2021
Immune Cells Help Brain Tumors Spread, but We Can Stop Them
Researchers have discovered how a glitch in the brain’s immune system can inadvertently cause an accelerated growt ...
MAY 20, 2021
Technology
Brain Imaging May Predict Pediatric Response to Anxiety Medication: Study
MAY 20, 2021
Brain Imaging May Predict Pediatric Response to Anxiety Medication: Study
According to the Centers for Disease Control (CDC), an estimated 4.4 million children ages 3 to 17 have been diagnosed w ...
JUN 27, 2021
Cell & Molecular Biology
Organoids Reveal Common Mechanism Underlying Rare Disorders
JUN 27, 2021
Organoids Reveal Common Mechanism Underlying Rare Disorders
Genetic testing has shown that mutations in a gene called HUWE1 are connected to rare syndromes that cause developmental ...
JUL 05, 2021
Cannabis Sciences
Prenatal Cannabis Exposure Lessens Effects of Antidepressants
JUL 05, 2021
Prenatal Cannabis Exposure Lessens Effects of Antidepressants
Researchers at Indiana University have found that mice exposed to cannabinoids while in the womb are less responsive to ...
JUL 12, 2021
Health & Medicine
Is Caffeine Good or Bad for Migraines?
JUL 12, 2021
Is Caffeine Good or Bad for Migraines?
The short answer is it's still not certain if caffeine helps or worsens migraines, but chronic consumption of caffei ...
JUL 07, 2021
Genetics & Genomics
How Double-Stranded DNA May Play a Critical Role in Memory and Recall
JUL 07, 2021
How Double-Stranded DNA May Play a Critical Role in Memory and Recall
Breaks in DNA are typically associated with harmful conditions, and the cell has ways to repair this damage. But it's be ...
Loading Comments...