Deep in the human brain, a very specific kind of cell dies during Parkinson’s disease.

For the first time, researchers have sorted large numbers of human brain cells in the substantia nigra into 10 distinct types. Just one is especially vulnerable in Parkinson’s disease, the team reports May 5 in Nature Neuroscience. The result could lead to a clearer view of how Parkinson’s takes hold, and perhaps even ways to stop it.

The new research “goes right to the core of the matter,” says neuroscientist Raj Awatramani of Northwestern University Feinberg School of Medicine in Chicago. Pinpointing the brain cells that seem to be especially susceptible to the devastating disease is “the strength of this paper,” says Awatramani, who was not involved in the study.

Parkinson’s disease steals people’s ability to move smoothly, leaving balance problems, tremors and rigidity. In the United States, nearly 1 million people are estimated to have Parkinson’s. Scientists have known for decades that these symptoms come with the death of nerve cells in the substantia nigra. Neurons there churn out dopamine, a chemical signal involved in movement, among other jobs (SN: 9/7/17).

But those dopamine-making neurons are not all equally vulnerable in Parkinson’s, it turns out.

“This seemed like an opportunity to … really clarify which kinds of cells are actually dying in Parkinson’s disease,” says Evan Macosko, a psychiatrist and neuroscientist at Massachusetts General Hospital in Boston and the Broad Institute of MIT and Harvard.
The tricky part was that dopamine-making neurons in the substantia nigra are rare. In samples of postmortem brains, “we couldn’t survey enough of [the cells] to really get an answer,” Macosko says. But Abdulraouf Abdulraouf, a researcher in Macosko’s laboratory, led experiments that sorted these cells, figuring out a way to selectively pull the cells’ nuclei out from the rest of the cells present in the substantia nigra. That enrichment ultimately led to an abundance of nuclei to analyze.

By studying over 15,000 nuclei from the brains of eight formerly healthy people, the researchers further sorted dopamine-making cells in the substantia nigra into 10 distinct groups. Each of these cell groups was defined by a specific brain location and certain combinations of genes that were active.

When the researchers looked at substantia nigra neurons in the brains of people who died with either Parkinson’s disease or the related Lewy body dementia, the team noticed something curious: One of these 10 cell types was drastically diminished.

These missing neurons were identified by their location in the lower part of the substantia nigra and an active AGTR1 gene, lab member Tushar Kamath and colleagues found. That gene was thought to serve simply as a good way to identify these cells, Macosko says; researchers don’t know whether the gene has a role in these dopamine-making cells’ fate in people.

The new finding points to ways to perhaps counter the debilitating diseases. Scientists have been keen to replace the missing dopamine-making neurons in the brains of people with Parkinson’s. The new study shows what those cells would need to look like, Awatramani says. “If a particular subtype is more vulnerable in Parkinson’s disease, maybe that’s the one we should be trying to replace,” he says.

In fact, Macosko says that stem cell scientists have already been in contact, eager to make these specific cells. “We hope this is a guidepost,” Macosko says.

The new study involved only a small number of human brains. Going forward, Macosko and his colleagues hope to study more brains, and more parts of those brains. “We were able to get some pretty interesting insights with a relatively small number of people,” he says. “When we get to larger numbers of people with other kinds of diseases, I think we’re going to learn a lot.”

For many recreational runners, taking a jog is a fun way to stay fit and burn calories. But it turns out an individual has a tendency to settle into the same, comfortable pace on short and long runs — and that pace is the one that minimizes their body’s energy use over a given distance.

“I was really surprised,” says Jessica Selinger, a biomechanist at Queen’s University in Kingston, Canada. “Intuitively, I would have thought people run faster at shorter distances and slow their pace at longer distances.”

Selinger and colleagues combined data from more than 4,600 runners, who went on 37,201 runs while wearing a fitness device called the Lumo Run, with lab-based physiology data. The analysis, described April 28 in Current Biology, also shows that it takes more energy for someone to run a given distance if they run faster or slower than their optimum speed.
“There is a speed that for you is going to feel the best,” Selinger says. “That speed is the one where you’re actually burning fewer calories.”

The runners ranged in age from 16 to 83, and had body mass indices spanning from 14.3 to 45.4. But no matter participants’ age, weight or sex — or whether they ran only a narrow range of distances or runs of varying lengths — the same pattern showed up in the data repeatedly.

Researchers have thought that running was performance-driven, says Melissa Thompson, a biomechanist at Fort Lewis College in Durango, Colo., who was not involved in the new study. This new research, she says, is “talking about preference, not performance.”

Most related research, Selinger says, has been done in university laboratories, with study subjects who are generally younger and healthier than the general population. By using wearable devices, the researchers could track many more runs, across more real-life conditions than is possible in a lab. That allowed the scientists to look at a “much broader cross section of humanity,” she says. Treadmill tests measuring energy use at different paces with people representative of those included in the fitness tracker data were used to determine optimum energy-efficient speeds.

Because the study includes a wide range of conditions and doesn’t control for things like fasting before running, it’s messier than data gathered in labs. Still, the sheer volume of real-world runs recorded by the wearable devices supports a convincing general rule about how humans run, says Rodger Kram, a physiologist at the University of Colorado Boulder not involved with the study. “I think the rule’s right.”

The results don’t apply to very long runs when fatigue starts to set in, or to race performance by elite athletes or others consciously training for speed. And a runner’s optimum pace can change over time, with training or age for instance.

There are quick tricks for those who want to speed up and go for a little more calorie burn to temporarily trump their body’s natural inclinations: Listen to upbeat music or jog alongside someone with a faster pace, Selinger says. “But it seems like your preference is actually to sink back into that optimum.”

The results match observations of optimum pacing from animals like horses and wildebeests, and also correspond to the way humans tend to walk at a speed that minimizes their individual energy use (SN: 9/10/15).

It does make sense that humans would be adapted to run at an optimum speed for minimizing energy use, says coauthor Scott Delp, a biomechanist at Stanford University. Imagine being an early human ancestor going out to hunt difficult prey. “It might be days before I get my next food,” he says. “So I want to spend the least energy en route to getting that food.”

An act of acrobatics keeps males of one orb-weaving spider species from becoming their mates’ post-sex snack.

After mating, Philoponella prominens males catapult away from females at speeds up to nearly 90 centimeters per second, researchers report April 25 in Current Biology. Other spiders jump to capture prey or avoid predators (SN: 3/16/19). But P. prominens is unique among spiders in that males soar through the air to avoid sexual cannibalism, the researchers say.

P. prominens is a social species that’s native to countries such as Japan and Korea. Up to 300 individual spiders can come together to weave an entire neighborhood of webs. While studying P. prominens’ sexual behavior, arachnologist Shichang Zhang and colleagues noticed that sex seemed to always end with a catapulting male. But the movement was “so fast that common cameras could not record the details,” says Zhang, of Hubei University in Wuhan, China.

High-resolution video of mating partners clocked the male arachnids’ speed from around 32 cm/s to 88 cm/s, the researchers report. That’s equal to just under 1 mile per hour to nearly 2 mph.
The jump looks a little like the start of a backstroke swimming race, Zhang says. Males hold the tips of their front legs against a female’s body. The spiders then use hydraulic pressure to extend a joint in those legs, quickly launching a male off a female before she can capture and eat him.

Of 155 successful mating rituals that the researchers observed, 152 males catapulted to survival. The remaining three that didn’t fell victim to their partner. Female spiders also ate all 30 males that the team stopped from jumping to freedom with a paintbrush.

These male orb weavers probably acquired their jumping abilities to counter females’ cannibalistic tendencies, Zhang says. The spiders’ leap to survival is a “fantastic kinetic performance.”