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Brainstem neurons that regulate disease symptoms found in mouse model

Brainstem neurons that regulate disease symptoms found in mouse model
Written by adrina

−1) injection. n = 4 for each group except 24 h after LPS, for which n = 3. b, Heat map of log2[fold change] for LPS versus saline in the indicated regions at each time point. Only regions with at least one significant change at any time point (False Discovery Rate-adjusted P<0.05) are shown. Left color bar, brain subdivision; CTXsp, cortical subplate; STR, striatum; PAL, pallidum; MB, midbrain; AP and NTS are displayed. c,d, Representative images of FOS expression 3 h after injection of saline (c) and LPS (d). The right panels show a higher magnification view of the NTS-AP region outlined in the left panels. Scale bar, 1 mm (left) or 250 μm (right). e, From left to right: NTS and AP in Allen Brain Atlas (ABA), ClearMap output of significant changes (false discovery rate adjusted P<0.05, red) for post-LPS (3 h) versus saline injection, ClearMap-generated mean heatmap of FOS counts for saline injection (n=4) and ClearMap-generated mean heatmap of FOS counts for LPS injection (3 h, n=4). f,g, FOS counts for NTS (f) and AP (g), for indicated treatments (LPS concentration, 0.5 mg kg−1) and times; Output of ClearMap. Error bars represent sem. The mouse illustration in a was created with BioRender.com. Recognition: Nature (2022). DOI: 10.1038/s41586-022-05161-7″ width=”800″ height=”530″/>
Brain-wide activity changes during disease behavior. a, Timeline for sampling and subsequent whole-brain imaging of FOS. Samples (circled numbers) were taken at the indicated time points after saline or LPS (0.5 mg kg−1) injection. n = 4 for each group except 24 h after LPS, for which n = 3. b, Heat map of log2[fold change] for LPS versus saline in the indicated regions at each time point. Only regions with at least one significant change at any time point (false discovery rate-adjusted P−1) and time points; Output of ClearMap. Error bars represent sem. The mouse illustration in a was created with BioRender.com. Recognition: Nature (2022). DOI: 10.1038/s41586-022-05161-7

A team of researchers from Rockefeller University, in collaboration with a colleague from Fudan University, has found the clusters of neurons in the mouse brain that regulate disease symptoms. In her article published in the journal Naturethe group describes the multi-step process they undertook to locate the nerve bundles and why finding them might be important. Amirah-Iman Hicks and Masha Prager-Khoutorsky of McGill University published an article in News & Views in the same journal issue describing the work.

When humans (or mice) get sick, they tend to show symptoms such as fever, pain, and nausea. Previous research has shown that the body produces such symptoms to fight whatever is behind the disease. But how the brain carries out these activities is still unknown. In this new experiment, the researchers examined mice showing symptoms of the disease.

The researchers first injected them with lipopolysaccharide, a bacterial endotoxin, rather than infecting them directly — this allowed for more consistent symptoms. They then performed multiple brain scans on the mice over a 24-hour period to learn more about what was happening in the brain when it triggered symptoms of the disease. They found that shortly after the first injection, a subset of neurons in the brainstem called the nucleus of the tract (NTS) became active, as did the area postrema (AP). Previous research has shown that the NTS receives signals from the colon and the AP is constantly bathed in humoral factors.

The researchers then used a technique called TRAP2 to activate the neural cluster in test mice that did not receive lipopolysaccharide injections. These mice showed the same symptoms of the disease as the mice that received the injections. They also found that inhibiting the nerve groups in mice that received the injection greatly reduced disease symptoms.

Next, the researchers performed RNA sequencing on the cells in the nerve clusters they identified, allowing them to identify the specific neurons within the clusters they identified that were responsible for triggering disease symptoms.

The researchers need to probe to make sure the same parts of the human brain are involved as the nerve clusters they found in the mice. And if things go as planned, they suggest their work could lead to new types of drugs to relieve symptoms from disease.


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More information:
Anoj Ilanges et al., Brainstem ADCYAP1+ neurons control multiple aspects of disease behavior, Nature (2022). DOI: 10.1038/s41586-022-05161-7

Amirah-Iman Hicks et al, Neural Perpetrators of Illness Behavior, Nature (2022). DOI: 10.1038/d41586-022-02321-7

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Citation: Brainstem Neurons Regulating Disease Symptoms Found in Mouse Model (2022 September 14) Retrieved September 14, 2022 from https://medicalxpress.com/news/2022-09-neurons-brainstem-illness-symptoms-mouse .html

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