Traffic jams in the brain

It was really exciting to see that such traffic jams can happen among the tiny cargo in the brain, says Parul Sood.

It was really exciting to see that such traffic jams can happen among the tiny cargo in the brain, says Parul Sood.

Neurons transport cargo of various sizes constantly, and many times, this can lead to traffic jams. A new study of the roundworm (Caenorhabditis elegans) and fruitfly (Drosophila) shows that such traffic jams can be due to purely physical constraints, not involving any chemical signalling processes. Such stalling of cargo can happen in neurons afflicted by neurodegenerative diseases.

A recent study shows that it can happen even in normal cells. This could be a method adopted by the neuron to regulate the flow of mitochondria, vesicles containing neurotransmitters, and the like, along the length of its axon. The axon is the long arm of the neuron, which reaches out to the synapse or nerve endings. The study is published in the journal Traffic.

The researchers compare this to Indian roads. On the road, there are vehicles of several sizes and people walking, all moving on the same narrow lane. If one of these vehicles should stop for some reason, traffic tends to pile up temporarily. It eases out once the vehicle moves on and the traffic jam is cleared. Similar traffic jams of cargo happen in the axon.

Eureka moment

“It was really exciting to see that such traffic jams can happen among the tiny cargo in the brain,” says Parul Sood, first author of the paper, who is a research scholar at Tata Institute of Fundamental Research in Mumbai. When the team was brainstorming to find a way of demonstrating this, she had a “Eureka!” moment: “I quickly went through my data to see if vesicles rushed through the location from where a stationary cargo — the presumed physical block — mobilised, and they did, showing that indeed vesicle motion was physically blocked at that location!”

Apart from the cargo, there are bits of cytoskeleton floating in the body of the axon. This includes microtubules, which are like roads for the cargo to move along. The cargo can halt for any reason, it could be that it has fallen off a microtubule or that it has arrived at the end of the microtubule, or some other reason, leading to an accumulation of cargo.

Dr Sandhya Koushika of TIFR, Mumbai, a co-author, and in whose lab the experiments were performed, explains, “We found that there were particular locations in the cell which were susceptible to forming these accumulations. The most susceptible regions were those that were actin-rich. When you have concentrations of actin, in this region when the cargo stalls, it’s a double whammy. The amount of space allowed for the cargo to move has really shrunk.”

Regulating mechanism

This could be a way to regulate the traffic down the axon. Dr Gautam Menon, from The Institute of Mathematical Sciences, a co-author of the paper, draws an analogy to the Mumbai-Chennai highway. “Suppose you are making things in Mumbai and sending them down to Chennai. Now suppose you want more stuff, you don’t want to send a signal all the way up to Mumbai,” he says. An efficient way to regulate this is to park it along the way in different locations, and summon the cargo when needed. This is not a static accumulation but dynamic.

“Many people, especially biologists, are not greatly attracted to the idea that you may not have classical regulation… [where] something turns on, something turns off and there are changes in levels of protein etc. Here we show it can happen in perfectly healthy neurons with no changes in levels of proteins,” adds Dr Koushika.

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Printable version | Jun 11, 2022 1:38:48 pm |