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Observing stroke recovery in mice may provide guide for humans

  • Scientists have observed genes responsible for helping mice recover from strokes.
  • This could provide guidance for humans.
  • Drugs could be developed to target these specific genes.

Scientists at Stanford Medicine recently observed that some mice recovered from strokes better than others, leading them to wonder whether or not they could find evidence that specific genes played a role in recovery. They did.

The results of the study — which can be read here — describes thirty-three male mice with strokes and seven mice without strokes being charged with balancing on a "horizontal rotating beam" — running out across and back. After the stroke, the mice couldn't do this. Two weeks after the stroke, 25% of the mice were able to recover well enough to run across the length of the beam and back.

Previous research into stroke recovery in mice has noted that sensory deprivation has pushed its brain in a more healthy direction if its whiskers were trimmed; blocking an immune response aids stroke recovery; Ambien can aid in recovery; there's research that talks about a rich, playful environment aiding in a mouse's recovery, which is featured in the video below; and even a grape-rich diet can help improve stroke recovery in mice.

Why look at genetic recovery in mice? "Understanding the genes regulated post-stroke could help us design novel ways to treat patients in the days and weeks after the initial event," Michelle Y. Cheng is quoted as saying.

What was found? "Distinct biological pathways" in the portion of the motor cortex opposite the lesion wrought by the stroke as well as pathways on the same side of lesion-affected cortex. There were 38 genes on the side of the brain impacted by the lesion associated with recovery and 74 genes opposite the lesion that were associated with recovery.

A majority of these genes are involved with something called cAMP signaling. cAMP signaling detects molecules outside already existing cells and has a role in determining a response.

'cAMP signalling' activates a protein called a protein kinase that modifies other proteins in the body that send signals off somewhere else. Broadly speaking, cAMP signalling also has a role in memory, water absorbed in the kidney, whether or not the heart is relaxed, breaking down fats, and more.

The particular genes involved in cAMP signalling that played a role in stroke recovery for the mice are called adenosine receptor A2A, dopamine receptor D2, and phosphodiesterase 10A. Receptors are protein molecules embedded in cell membranes that respond to external stimuli to transmit information somewhere else. The A2A is often a target of caffeine. It is a protein that is abundant in platelets, lymphocytes, and more. The D2 receptor is typically the target of most antipsychotic drugs. Current research suggests that there might be a link between phosphodiesterase 10A and obesity.

In the case of post-stroke recovery, however, the study notes that activating A2A "signaling within a few hours poststroke can reduce inflammatory cell infiltration after stroke"; that "activation of Drd2 on astrocytes in acute stroke can reduce neuroinflammation"; and that "inhibition of Pde10a may be a promising therapeutic strategy for psychiatric and neurodegenerative diseases."

There are complications — blocking A2A signaling can help against a lesion-induced toxicity; and not only does Drd2 inhibit cAMP communicating with the rest of the body, but "the role of Drd2 in brain repair is also unclear."

Nevertheless, this is research that makes the figurative target of our interest a little clearer and a little sharper, illustrating where medicine can take aim next.

Hulu's original movie "Palm Springs" is the comedy we needed this summer

Andy Samberg and Cristin Milioti get stuck in an infinite wedding time loop.

Gear
  • Two wedding guests discover they're trapped in an infinite time loop, waking up in Palm Springs over and over and over.
  • As the reality of their situation sets in, Nyles and Sarah decide to enjoy the repetitive awakenings.
  • The film is perfectly timed for a world sheltering at home during a pandemic.
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Two MIT students just solved Richard Feynman’s famed physics puzzle

Richard Feynman once asked a silly question. Two MIT students just answered it.

Surprising Science

Here's a fun experiment to try. Go to your pantry and see if you have a box of spaghetti. If you do, take out a noodle. Grab both ends of it and bend it until it breaks in half. How many pieces did it break into? If you got two large pieces and at least one small piece you're not alone.

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Our ‘little brain’ turns out to be pretty big

The multifaceted cerebellum is large — it's just tightly folded.

Image source: Sereno, et al
Mind & Brain
  • A powerful MRI combined with modeling software results in a totally new view of the human cerebellum.
  • The so-called 'little brain' is nearly 80% the size of the cerebral cortex when it's unfolded.
  • This part of the brain is associated with a lot of things, and a new virtual map is suitably chaotic and complex.

Just under our brain's cortex and close to our brain stem sits the cerebellum, also known as the "little brain." It's an organ many animals have, and we're still learning what it does in humans. It's long been thought to be involved in sensory input and motor control, but recent studies suggests it also plays a role in a lot of other things, including emotion, thought, and pain. After all, about half of the brain's neurons reside there. But it's so small. Except it's not, according to a new study from San Diego State University (SDSU) published in PNAS (Proceedings of the National Academy of Sciences).

A neural crêpe

A new imaging study led by psychology professor and cognitive neuroscientist Martin Sereno of the SDSU MRI Imaging Center reveals that the cerebellum is actually an intricately folded organ that has a surface area equal in size to 78 percent of the cerebral cortex. Sereno, a pioneer in MRI brain imaging, collaborated with other experts from the U.K., Canada, and the Netherlands.

So what does it look like? Unfolded, the cerebellum is reminiscent of a crêpe, according to Sereno, about four inches wide and three feet long.

The team didn't physically unfold a cerebellum in their research. Instead, they worked with brain scans from a 9.4 Tesla MRI machine, and virtually unfolded and mapped the organ. Custom software was developed for the project, based on the open-source FreeSurfer app developed by Sereno and others. Their model allowed the scientists to unpack the virtual cerebellum down to each individual fold, or "folia."

Study's cross-sections of a folded cerebellum

Image source: Sereno, et al.

A complicated map

Sereno tells SDSU NewsCenter that "Until now we only had crude models of what it looked like. We now have a complete map or surface representation of the cerebellum, much like cities, counties, and states."

That map is a bit surprising, too, in that regions associated with different functions are scattered across the organ in peculiar ways, unlike the cortex where it's all pretty orderly. "You get a little chunk of the lip, next to a chunk of the shoulder or face, like jumbled puzzle pieces," says Sereno. This may have to do with the fact that when the cerebellum is folded, its elements line up differently than they do when the organ is unfolded.

It seems the folded structure of the cerebellum is a configuration that facilitates access to information coming from places all over the body. Sereno says, "Now that we have the first high resolution base map of the human cerebellum, there are many possibilities for researchers to start filling in what is certain to be a complex quilt of inputs, from many different parts of the cerebral cortex in more detail than ever before."

This makes sense if the cerebellum is involved in highly complex, advanced cognitive functions, such as handling language or performing abstract reasoning as scientists suspect. "When you think of the cognition required to write a scientific paper or explain a concept," says Sereno, "you have to pull in information from many different sources. And that's just how the cerebellum is set up."

Bigger and bigger

The study also suggests that the large size of their virtual human cerebellum is likely to be related to the sheer number of tasks with which the organ is involved in the complex human brain. The macaque cerebellum that the team analyzed, for example, amounts to just 30 percent the size of the animal's cortex.

"The fact that [the cerebellum] has such a large surface area speaks to the evolution of distinctively human behaviors and cognition," says Sereno. "It has expanded so much that the folding patterns are very complex."

As the study says, "Rather than coordinating sensory signals to execute expert physical movements, parts of the cerebellum may have been extended in humans to help coordinate fictive 'conceptual movements,' such as rapidly mentally rearranging a movement plan — or, in the fullness of time, perhaps even a mathematical equation."

Sereno concludes, "The 'little brain' is quite the jack of all trades. Mapping the cerebellum will be an interesting new frontier for the next decade."

Economists show how welfare programs can turn a "profit"

What happens if we consider welfare programs as investments?

A homeless man faces Wall Street

Spencer Platt/Getty Images
Politics & Current Affairs
  • A recently published study suggests that some welfare programs more than pay for themselves.
  • It is one of the first major reviews of welfare programs to measure so many by a single metric.
  • The findings will likely inform future welfare reform and encourage debate on how to grade success.
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Videos

Unhappy at work? How to find meaning and maintain your mental health

Finding a balance between job satisfaction, money, and lifestyle is not easy.

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