Neuron: Precise positioning! Make the body's biological clock work properly.

In a new study published in Neuron on Aug. 8, a team from the University of Texas Southwestern Medical Center (UTSW) developed a bioluminescent circadian rhythm genetically engineered mouse and related imaging system that visualizes biological clock fluctuations in mouse cells.
gives us a new understanding of which brain cells play an important role in maintaining the body's biological clock.
team, the method could also be widely used to answer questions about the daily rhythms of cells throughout the body.
"This is a very important technical resource for advancing circadian rhythms, and you can use these mice for many different studies," said Joseph Takahashi, lead author of the study and head of the UTSW Department of Neuroscience and a researcher at the Howard Hughes School of Medicine (HHMI).
" it is well known that almost every cell in humans and mice has an internal biological clock that fluctuates over a period of about 24 hours.
these cells not only help alert to hunger and sleep cycles, but also help indicate biological functions such as immunity and metabolism.
biological clock defects have been linked to diseases such as cancer, diabetes, Alzheimer's disease and sleep disorders.
it is known that the visual cross-core (SCN) in the brain, called a circadian rhythm pacemaker, integrates information from the eye about the ambient bright and dark cycles with the body's master clock.
, SCN helps keep the rest of the cells in the body in sync.
SCN is a very special clock because it's both robust and compact," says Takahashi, a 20-year-old.
it's a very powerful pacemaker that doesn't forget the time, but at the same time it can vary according to the seasons, change the length of the day, or travel between time zones.
to study the biological clocks of SCN and other parts of the body, Takahashi's team previously developed a mouse with a bioluminescent version of PER2.
PER2 is a key circadian rhythm protein whose levels fluctuate through the day.
by looking at changes in bioluminescence levels, the researchers were able to observe how PER2 circulates in animals during the day.
but for humans, the protein is present in almost every part of the body, and it is sometimes difficult to distinguish between different cell types mixed together in the same tissue.
, for example, if you look at brain slices, almost every cell has a PER2 signal, so you can't really tell where a particular PER2 signal comes from," says Takahashi.
in the new study, researchers used a new bioluminescence system that changes color from red to green only in cells that express a specific gene called Cre.
, the researchers genetically modified mice so that Cre, which is not naturally present in mouse cells, appears in only one cell type at a time.
to test the usefulness of this method, the team studied two types of cells that make up the brain SCN, arginine pressurin (AVP) and vascular active intestinal polypeptides (VIPs).
past, scientists hypothesed that VIP neurons were the key to keeping the rest of the SCN in sync.
when the team looked at VIP neurons that express only Cre in cells, PER2 glowed green in VIP cells and red elsewhere.
they found that removing the circadian rhythm gene from neurons had little overall effect on the circadian rhythms of VIP neurons or the rest of the SCN.
Dr Yongli Shan, lead author of the study and a researcher at the UTSW Institute, explained: "Even if VIP neurons no longer have a normal clock, the rest of the SCN exhibits essentially the same behavior, with nearby cells sending signals to VIP neurons to keep them in sync with the rest of the SCN."
"When they repeated the same experiment on AVP neurons, removing key clock genes, they found that not only were the rhythms of AVP neurons themselves disrupted, but the entire SCN network stopped the normal 24-hour rhythmic synchronization cycle.
showed us that the clock of AVP neurons is critical to synchronization across the SCN network," shan said.
this is a surprising result and a bit counterintuitive, so we hope it will lead to more research on AVP neurons.
Takahashi said other researchers who study circadian rhythms have used his lab's mouse line to study the daily cycles of other cells.
the mice could give scientists insight into the differences in circadian rhythms between cell types in a single organ, or study differences in the way tumor cells circulate with healthy cells.
In a variety of complex or lesions tissues, it allows you to see which cells have rhythms and how they are similar or different from other cell types," he said.
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