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
JUN 01, 2020
Neuroscience
What Causes 'Good' and 'Bad' Trips in the Brain
JUN 01, 2020
What Causes 'Good' and 'Bad' Trips in the Brain
People who use psychedelics like magic mushrooms, LSD and DMT often describe a feeling of going 'beyond their human ...
JUN 02, 2020
Cannabis Sciences
Ancient Israelites Used Cannabis to Experience God
JUN 02, 2020
Ancient Israelites Used Cannabis to Experience God
Researchers have found evidence that ancient worshipers in Israel may have used cannabis to experience God over 2800 yea ...
JUL 19, 2020
Cell & Molecular Biology
Neurons and Blood Vessels 'Talk' About Cell Fate
JUL 19, 2020
Neurons and Blood Vessels 'Talk' About Cell Fate
Scientists have used a zebrafish model to show that the neurons of the peripheral nervous system communicate with blood ...
JUL 19, 2020
Neuroscience
Eating Fish May Protect Brain from Air Pollution
JUL 19, 2020
Eating Fish May Protect Brain from Air Pollution
Researchers have found that a diet high in omega-3 fatty acids may prevent neurodegeneration among older women living in ...
JUL 22, 2020
Clinical & Molecular DX
Unmasking the Secrets of the Substantia Nigra to Diagnose Parkinson's
JUL 22, 2020
Unmasking the Secrets of the Substantia Nigra to Diagnose Parkinson's
Parkinson’s disease is a devastating condition whereby neurons in a specific region of the brain that controls mov ...
JUL 26, 2020
Neuroscience
How COVID-19 Causes Loss of Smell
JUL 26, 2020
How COVID-19 Causes Loss of Smell
Temporary loss of smell, known as anosmia, is one of the most common early indicators of COVID-19. Although some say it ...
Loading Comments...