Tag Archives: glia

Microglia.

Researchers capture first ever images of microglia eating brain synapses

It’s not just zombies that chow on brains — for the first time, researchers have filmed microglia chowing down on brain synapses.

Synapse.

Image credits Savant-fou / Wikimedia.

Brains, like pretty much like your room, tends to get messy. Unlike your room, however, the brain has specialized support cells, a class known as “glia“, to keep everything working — and one type of glia, named “microglia” because they’re quite tiny, act as the brain’s Roombas, keeping it tidy 24/7.

While we knew, in theory, what these microglia were up to, we’ve never actually seen them go about their business. Not until recently, however, when researchers from the European Molecular Biology Laboratory (EMBL) captured them in the act.

“You finished with that?”

Neurons are arguably one of the most important cells in the brain; they’re the ones that process information and perform the job the brain is meant to do. However, the real heavy lifting inside this organ is performed by glia. And they’re quite prolific: our brains are roughly 70% glia, and around 10% of all cells in your brain are microglia specifically.

Microglia are related to macrophages — the variety of white cell that ‘eat’ bad guys. Microglia perform a similar function in the brain, acting as the main active component of its immune system. But they also take an active part in steering brain development; while not fighting anyone, microglia weed out brain synapses that have outlived their usefulness or just to make room for newer, more efficient synapses.

Given their massively influential role in the brain, it’s understandable why researchers have been trying to get a look at microglia in action for a long time now. Researchers from EMBL Rome, led by Laetitia Weinhard, working in collaboration with EMBL Heidelberg, are the first to actually succeed at this task. They set up a massive imaging study to capture the process in action in mouse brains.

The team combined two brain imaging techniques, correlative light and electron microscopy (CLEM), with light sheet fluorescence microscopy — a technique developed at EMBL — to capture the first images of microglia eating synapses.

Microglia.

Multiple synapse heads send out filopodia (green) converging on one microglia (red), as seen by focused ion beam scanning electron microscopy. L. Weinhard, EMBL Rome

One surprising finding was that around half of the interactions between microglia and synapses prompted the latter to send out thin projections or ‘filopoda’, as if to greet the cell, the team notes. In one case, the researchers observed no fewer than fifteen synapse heads extending filopoda toward a single microglia as it chowed on another synapse.

“Our findings suggest that microglia are nibbling synapses as a way to make them stronger, rather than weaker,” says Cornelius Gross (EMBL Rome), who led the research.

“As we were trying to see how microglia eliminate synapses, we realised that microglia actually induce their growth most of the time,” Laetitia Weinhard adds.

One other important find is that microglia could underly the formation of double synapses, where one neuron releases neurotransmitters to two others (instead of the traditional one-on-one communication). This mechanism shows that microglia are deeply involved in brain processes such as structural plasticity and can even induce the rearrangement of synapses — a process that underpins learning and memory.

The observations are the product of five years of technological development. During this time, the team worked with three different cutting-edge imaging systems before obtaining the images.

“This is what neuroscientists fantasised about for years, but nobody had ever seen before,” says Cornelius Gross. “These findings allow us to propose a mechanism for the role of microglia in the remodeling and evolution of brain circuits during development.”

Next, the team plans to investigate what role microglia play in brain development during adolescence, or if there’s any link between these cells and mental diseases.

Image: Flickr // angeladellatorre]

Mice with half human brains are smarter, some healthier

Oh, boy. This week’s freaky science story comes from the University of Rochester Medical Center in New York where researchers grafted mouse pups with human glial cells. Within one year, half the brain cells of the by now adult mice were human. A study made last year by the same team suggests that mice whose brains contain human glial cells are smarter, while another experiment seems to indicate that mice with defects like uninsulated nerves can repair these nerves if human brain cells are inserted.

The overlooked glia

supermice

Image: Scientific American

It’s important to set one thing straight: the mice still kept their 100% originally sourced neurons. It’s the glial cells that were human. Although there are about 100 billion neurons in the brain – the human one –  there may be about 10 to 50 times that many glial cells. So, why haven’t you heard about them before if they’re so important? You know how fads come and go…

Sure, neurons are the rock stars because they have firing ability and are responsible for all the signaling that goes inside the brain. Without glial cells, however, neurons would never be able to function. There are five types of glia:

  • Astrocyte (Astroglia): Star-shaped cells that provide physical and nutritional support for neurons: 1) clean up brain “debris”; 2) transport nutrients to neurons; 3) hold neurons in place; 4) digest parts of dead neurons; 5) regulate content of extracellular space
  • Microglia: Like astrocytes, microglia digest parts of dead neurons.
  • Oligodendroglia: Provide the insulation (myelin) to neurons in the central nervous system.
  • Satellite Cells: Physical support to neurons in the peripheral nervous system.
  • Schwann Cells: Provide the insulation (myelin) to neurons in the peripheral nervous system.

Steve Goldman of the University of Rochester Medical Center in New York extracted infant glia from donated human embryos and injected these into the brains of mouse pups. Soon enough, the glia started developing into astrocytes, which strengthen the connection between neuron connections called synapses. Human astrocytes are 10 to 20 times the size of mouse astrocytes and carry 100 times as many tendrils.

Taking over

Image: Wikimedia Commons

Image: Wikimedia Commons

Initially, some 300,000 human glia were inserted, but by the end of the year, the mouse had 12 million. This means that nearly all of the mouse’s native glia had been displaced.

“We could see the human cells taking over the whole space,” says Goldman. “It seemed like the mouse counterparts were fleeing to the margins.”

But do the human astrocytes in the mice actually behave as in the human brain or does the environment regulate them?

“That the cells work at all in a different species is amazing, and poses the question of which properties are being driven by the cell itself and which by the new environment,” says Wolfgang Enard of Ludwig-Maximilians University Munich in Germany, who has shown that mice are better at learning if they have the human Foxp2 gene, which has been linked with human language development.

This question will definitely be very interesting to answer. In a parallel experiment, Goldman and team inserted human glia once more into the brains of mice pups, only this time these bore a defect. The mice were poor at making myelin, the protein that insulates nerves.  Once again, the immature glia developed quickly, but this time something amazing happened:  many of the human glial cells matured into oligodendrocytes, brain cells that specialise in making the insulating material. Somehow, the glia recognized the defect and compensated.

[RELATED] Scientists engineer ‘super’ mice 

Multiple sclerosis is a terrible disease in which the myelin sheath is damaged, and the findings suggest that glia therapy might render positive results. In fact, Goldman applied for permission to treat MS patients with the glial progenitor cells, and hopes to start a trial in 12 to 15 months.

Is this still a mouse?

Image: Flickr // angeladellatorre]

Image: Flickr // angeladellatorre]

The same team made a similar experiment last year, only the human glia they inserted were mature. These became integrated into the mouse brain, but didn’t develop further or expanded in numbers. But here’s the interesting part. In a standardized memory test, mice remembered a sound associated with a mild electric shock  for four times as long as other mice when they heard the sound, suggesting their memory was about four times better.

“These were whopping effects,” says Goldman. “We can say they were statistically and significantly smarter than control mice.”

Next, to further determine how human astrocytes affect things like intelligence, memory or learning, Goldman will be grafting the same immature human glia into rat brains. Rats are smarter than mice, so it should be interesting to follow how the humanized rats respond.

Is this a super mouse? Is it a mouse anymore? Is it just a super smart mouse? Well, let’s leave it to Goldman:

“This does not provide the animals with additional capabilities that could in any way be ascribed or perceived as specifically human,” he says. “Rather, the human cells are simply improving the efficiency of the mouse’s own neural networks. It’s still a mouse.

Findings appeared in the Journal of Neuroscience.