Page 18 - Abacoa Community News - September '19

Page 18, Abacoa
Science On the cUtting edge

The Scripps Research Institute News

Scientists Discover neurons. Blocking of slowing memory

‘Forgetting’ Enzyme That one caspase enzyme, loss in conditions
such as Alzheimer’s
caspase 2, had a big
Lops Brain Cell Branches effect, increasing disease. Prior studies by
the density of Alzheimer’s researchers
An enzyme called caspase 2 plays dendritic spines to have shown that
a key role in cognition by helping a striking degree caspase 2 is produced
to remove unwanted connections, or that was obvious in at unusually high levels
synapses, between neurons in the brain, microscope images. A microscopic image of developing in the brains of people A centrifuge being loaded in a lab
a new study from scientists at the Florida The researchers neurons (Courtesy of the Baldwin Lab with this common form
campus of Scripps Research suggests. observed these at Scripps Research) of dementia, while mice engineered to develop an Alzheimer’s-
This “synapse pruning” process, spines at short like condition are somehow protected from the loss of synapses,
together with the opposing process intervals over two hours to confirm that blocking the enzyme dendritic spines, and memory when caspase 2 activity is blocked.
in which new synapses are formed, reduces the spine elimination rate without affecting the spine “We suspect that the caspase 2 signaling pathway may be
underlies everyday learning as well Professor Baoji Xu formation rate. When the scientists tried to induce spine shrinkage hijacked in Alzheimer’s to drive the synapse loss that correlates
as the healthy maturation of the brain in his lab artificially, using a standard method, blocking caspase 2 activity with memory impairment in this disease,” Xu says.
during childhood. The Scripps Research prevented the shrinkage. He and his colleagues now plan to study how caspase 2
scientists used a variety of experimental approaches, including These tests showed that caspase 2 is highly important for the normally is activated to prune neuronal connections during
behavioral studies in genetically engineered mice, to show that pruning of spines that accompanies synapse loss. The scientists in development and learning – and how it becomes abnormally
synapse pruning depends heavily on caspase 2. a further series of tests detailed the cascade of molecular signals activated in Alzheimer’s brains.
The discovery, published Aug. 9 in Nature Communications, that leads from caspase 2 activation to the weakening and loss In addition to Xu, the study’s co-authors were Zhi-Xiang Xu,
is a big step towards a better understanding of how the brain of synapses and spines. Ji-Wei Tan, Haifei Xu, Cassandra Hill, Olga Ostrovskaya, and
flexibly rewires itself during development and learning. It also Versions of caspase 2 are found throughout the animal Kirill Martemyanov, all of Scripps Research.
provides evidence for a possible new strategy – blocking caspase kingdom, which has long suggested to biologists that this enzyme The research was funded by the National Institutes of Health
2 activity – to treat Alzheimer’s disease and other memory has an important role conserved by evolution. That role, however, (grants NS073930, DK103335, K105954, and MH105482).
disorders in which brain connections are lost. has remained murky for decades – in part because “knockout” About Scripps Research
“Our study reveals a critical role for caspase 2 in cognitive mice bred without the caspase 2 gene do not show any obvious A leading nonprofit biomedical research institute, Scripps
flexibility and its underlying molecular mechanisms,” says study abnormalities. After their initial experiments, Xu and his team Research is ranked No. 1 in the world by Nature Index for
senior author Baoji Xu, Ph.D., professor in the Department of knew to look for more subtle abnormalities. They found, for scientific innovation. U.S. News and World Report consistently
Neuroscience at Scripps Research’s Florida campus. example, that caspase 2 knockout mice, compared to their ranks our graduate school in the top 10 in the United States.
Caspase enzymes are best known for their roles in apoptosis, a genetically intact littermates, have a similar increase in spine Our unique structure merges foundational studies in biology,
cellular self-destruct process that works, for example, to winnow density on the same types of neurons evaluated in the previous chemistry and computer science with translational research to
the neuronal population during brain development. Xu and his experiments. produce the next generation of drugs and advances in digital
colleagues wondered if caspases also are involved in the synapse A battery of behavioral tests also revealed that caspase 2 and precision medicine. On campuses in California and Florida,
pruning that occurs during development and learning. knockout mice, while normal in most respects, show a reduced scientists in the institute’s five academic research departments
In an initial set of tests, they blocked the activity of individual ability to forget things in certain contexts. For example, compared work hand-in-hand with researchers of the Scripps Research
caspase enzymes in cultured neurons taken from a memory to their intact littermates they appear to have more intense and Translational Institute and Calibr, our drug discovery division.
region in mouse brains. The aim was to see if that would lead to longer-lasting fear in standard fear-memory tests. We train the next generation of scientific leaders, expand the
an increase in root-like structures on the neurons called dendritic Apart from the light it sheds on a process of central importance frontiers of human knowledge and accelerate the development
spines, where synapses form and receive signals from other to brain function, the study points to the possibility of a new way of new medicines to improve lives around the planet.
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