Exercise alters brain chemistry to protect aging synapses

 

Couple jogging in the park

When elderly people stay active, their brains have more of a class of proteins that enhances the connections between neurons to maintain healthy cognition, a UC San Francisco study has found.

This protective impact was found even in people whose brains at autopsy were riddled with toxic proteins associated with Alzheimer's and other neurodegenerative diseases.

"Our work is the first that uses human data to show that synaptic protein regulation is related to physical activity and may drive the beneficial cognitive outcomes we see," said Kaitlin Casaletto, PhD, an assistant professor of neurology and lead author on the study, which appears in the January 7 issue of Alzheimer's & Dementia: The Journal of the Alzheimer's Association.

The beneficial effects of physical activity on cognition have been shown in mice but have been much harder to demonstrate in people.

Casaletto, a neuropsychologist and member of the Weill Institute for Neurosciences, worked with William Honer, MD, a professor of psychiatry at the University of British Columbia and senior author of the study, to leverage data from the Memory and Aging Project at Rush University in Chicago. That project tracked the late-life physical activity of elderly participants, who also agreed to donate their brains when they died.

"Maintaining the integrity of these connections between neurons may be vital to fending off dementia, since the synapse is really the site where cognition happens," Casaletto said. "Physical activity -- a readily available tool -- may help boost this synaptic functioning."

More Proteins Mean Better Nerve Signals

Honer and Casaletto found that elderly people who remained active had higher levels of proteins that facilitate the exchange of information between neurons. This result dovetailed with Honer's earlier finding that people who had more of these proteins in their brains when they died were better able to maintain their cognition late in life.

To their surprise, Honer said, the researchers found that the effects ranged beyond the hippocampus, the brain's seat of memory, to encompass other brain regions associated with cognitive function.

"It may be that physical activity exerts a global sustaining effect, supporting and stimulating healthy function of proteins that facilitate synaptic transmission throughout the brain," Honer said.

Synapses Safeguard Brains Showing Signs of Dementia

The brains of most older adults accumulate amyloid and tau, toxic proteins that are the hallmarks of Alzheimer's disease pathology. Many scientists believe amyloid accumulates first, then tau, causing synapses and neurons to fall apart.

Casaletto previously found that synaptic integrity, whether measured in the spinal fluid of living adults or the brain tissue of autopsied adults, appeared to dampen the relationship between amyloid and tau, and between tau and neurodegeneration.

"In older adults with higher levels of the proteins associated with synaptic integrity, this cascade of neurotoxicity that leads to Alzheimer's disease appears to be attenuated," she said. "Taken together, these two studies show the potential importance of maintaining synaptic health to support the brain against Alzheimer's disease."

The ‘surprisingly simple’ arithmetic of smell

 

Locust

Smell a cup of coffee.

Smell it inside or outside; summer or winter; in a coffee shop with a scone; in a pizza parlor with pepperoni -- even at a pizza parlor with a scone! -- coffee smells like coffee.

Why don't other smells or different environmental factors "get in the way," so to speak, of the experience of smelling individual odors? Researchers at the McKelvey School of Engineering at Washington University in St. Louis turned to their trusted research subject, the locust, to find out.

What they found was "surprisingly simple," according to Barani Raman, professor of biomedical engineering. Their results were published in the journal Proceedings of the National Academy of Sciences.

Raman and colleagues have been working with locusts for years, watching their brains and their behaviors related to smell in an attempt to engineer bomb-sniffing locusts. Along the way, they've made substantial gains when it comes to understanding the mechanisms at play when it comes to locusts' sense of smell.

To understand how it is that a locust can consistently recognize smells regardless of context, they took a cue from Ivan Pavlov. Like Pavlov's dogs, locusts were trained to associate an odor with food, their preference being a blade of grass. After going a day without food, a locust was exposed to a puff of odor (a puff of hexanol or isoamyl acetate), then given a blade of grass. In as few as six such presentations, the locust learned to open its palps (sensory appendages close to the mouth) in expectation of a snack after simply smelling the "training odorant." Just like us recognizing coffee, the trained locust could recognize the odor and did not let other factors get in the way.

At this point, researchers began looking at which neurons were firing when the locust was exposed to the odor under different conditions, including in conjunction with other smells, in humid or dry conditions, when they were starved or fully fed, trained or untrained, and for different amounts of time.

Under different circumstances, it turned out, researchers saw highly inconsistent patterns of neurons were activated even though the locust palps opened every time. "The neural responses were highly variable," Raman said. "That seemed to be at odds with what the locusts were doing, behaviorally."

How could variable neural responses produce consistent or stable behavior? To probe this, researchers turned to a machine-learning algorithm. "We wanted to see if given these variable neural response patterns, can we predict the locust behavior?" Raman said. "The answer was yes, we can."

The algorithm turned out to be very simple to interpret. It exploited two functional types of neurons: there are ON neurons, which are activated when an odorant is present, and there are OFF neurons, which are silenced when an odorant is present but become activated after the odor presentation ends.

"You can think of the ON neurons as conveying 'evidence for' an odor being present, and OFF neurons as 'evidence against' that odor being present," Raman said. To recognize an odorant's presence, researchers simply needed to add evidence for the odorant being present (i.e. add the spikes across all ON neurons) and subtract evidence against that odor being present (i.e. add the spikes across all OFF neurons). If the result was above a certain threshold, machine learning would predict the locust smelled the odor.

"We were surprised to find that this simple approach is all that was needed to robustly recognize an odorant," Raman said.

Raman likened the process to shopping for a shirt. Say you have a list of qualities you're looking for -- cotton, long sleeves, button-down, solid color, maybe a front pocket to hold your glasses -- and a few dealbreakers, such as dry-clean only or polka dots.

You may get lucky and find a shirt that is precisely what you are looking for. But, more pragmatically, you would make a purchase as long as many of the features you are looking for are present and the majority of features that are deal breakers are not presen

Chemists use DNA to build the world’s tiniest antenna

Researchers at Université de Montréal have created a nanoantenna to monitor the motions of proteins. Reported this week in Nature Methods, the device is a new method to monitor the structural change of proteins over time -- and may go a long way to helping scientists better understand natural and human-designed nanotechnologies.

"The results are so exciting that we are currently working on setting up a start-up company to commercialize and make this nanoantenna available to most researchers and the pharmaceutical industry," said UdeM chemistry professor Alexis Vallée-Bélisle, the study's senior author.

An antenna that works like a two-way radio

Over 40 years ago, researchers invented the first DNA synthesizer to create molecules that encode genetic information. "In recent years, chemists have realized that DNA can also be employed to build a variety of nanostructures and nanomachines," added the researcher, who also holds the Canada Research Chair in Bioengineering and Bionanotechnology.

"Inspired by the 'Lego-like' properties of DNA, with building blocks that are typically 20,000 times smaller than a human hair, we have created a DNA-based fluorescent nanoantenna, that can help characterize the function of proteins." he said

"Like a two-way radio that can both receive and transmit radio waves, the fluorescent nanoantenna receives light in one colour, or wavelength, and depending on the protein movement it senses, then transmits light back in another colour, which we can detect."

One of the main innovations of these nanoantennae is that the receiver part of the antenna is also employed to sense the molecular surface of the protein studied via molecular interaction.

One of the main advantages of using DNA to engineer these nanoantennas is that DNA chemistry is relatively simple and programmable," said Scott Harroun, an UdeM doctoral student in chemistry and the study's first author.

"The DNA-based nanoantennas can be synthesized with different lengths and flexibilities to optimize their function," he said. "One can easily attach a fluorescent molecule to the DNA, and then attach this fluorescent nanoantenna to a biological nanomachine, such as an enzyme.

"By carefully tuning the nanoantenna design, we have created five nanometer-long antenna that produces a distinct signal when the protein is performing its biological function."

Fluorescent nanoantennas open many exciting avenues in biochemistry and nanotechnology, the scientists believe.

"For example, we were able to detect, in real time and for the first time, the function of the enzyme alkaline phosphatase with a variety of biological molecules and drugs," said Harroun. "This enzyme has been implicated in many diseases, including various cancers and intestinal inflammation.

"In addition to helping us understand how natural nanomachines function or malfunction, consequently leading to disease, this new method can also help chemists identify promising new drugs as well as guide nanoengineers to develop improved nanomachines," added Dominic Lauzon, a co-author of the study doing his PhD in chemistry at UdeM.

One main advance enabled by these nanoantennas is also their ease-of-use, the scientists said.