Body temperature regulation: how fever comes

September 03, 2018

The appearance of fever is associated with the release in the hypothalamus of a lipid compound called prostaglandin E2 (PGE2), which has an important role in the regulation of body temperature. However, how PGE2 is supplied to or maintain in the brain, and the role of membrane transporters (in particular of the prostaglandin transporter OATP2A1, encoded by the gene SLCO2A1) in this process still needs to be elucidated.

To shed light on this question, Takeo Nakanishi at Kanazawa University, Japan, and colleagues performed a microdialysis study on mice, published in the Journal of Neuroscience. The researchers used mice with normal Slco2a1, with total Slco2a1 deficiency or with monocyte-/macrophage-specific Slco2a1 deficiency. They first injected the mice with physiological saline, observing the same body temperature for mice with and without SLCO2A1, indicating that the presence of OATP2A1 does not affect the basal body temperature. They then administered to the mice a pyrogen, lipopolysaccharide, that normally causes a fever. Indeed, mice with Slco2a1 developed a fever after 2h, whereas the pyrogenic effect of lipopolysaccharide was not observed in mice with total SLCO2A1 deficiency. They further demonstrate the body temperature of mice with monocyte-/macrophage-specific Slco2a1 deficiency was partially attenuated. Intriguingly, an inhibitor of OATP2A1 injected to the brain of rats with normal Slco2a1 inhibited the febrile response -- in this case only an initial rise in body temperature was observed.

The study reveals that the onset of fever is associated with increased PGE2 concentration in the hypothalamus interstitial fluid, but not in the cerebrospinal fluid, thus OATP2A1 seems to work by maintaining high levels of PGE2 in the hypothalamus, either by stimulating its secretion from glial cells in the hypothalamus and from brain capillary endothelial cells or by facilitating its transport through the blood-brain barrier. OATP2A1 seems to be involved in the secretion of PGE2 from macrophages, but OATP2A1 in cells other than macrophages may also contribute to the febrile response.

This newly gained insight of the mechanisms underlying the inflammatory response in the brain associated with fever might be used to develop new strategies for treatment, pointing to OATP2A1 as a useful therapeutic target.
-end-


Kanazawa University

Related Brain Articles from Brightsurf:

Glioblastoma nanomedicine crosses into brain in mice, eradicates recurring brain cancer
A new synthetic protein nanoparticle capable of slipping past the nearly impermeable blood-brain barrier in mice could deliver cancer-killing drugs directly to malignant brain tumors, new research from the University of Michigan shows.

Children with asymptomatic brain bleeds as newborns show normal brain development at age 2
A study by UNC researchers finds that neurodevelopmental scores and gray matter volumes at age two years did not differ between children who had MRI-confirmed asymptomatic subdural hemorrhages when they were neonates, compared to children with no history of subdural hemorrhage.

New model of human brain 'conversations' could inform research on brain disease, cognition
A team of Indiana University neuroscientists has built a new model of human brain networks that sheds light on how the brain functions.

Human brain size gene triggers bigger brain in monkeys
Dresden and Japanese researchers show that a human-specific gene causes a larger neocortex in the common marmoset, a non-human primate.

Unique insight into development of the human brain: Model of the early embryonic brain
Stem cell researchers from the University of Copenhagen have designed a model of an early embryonic brain.

An optical brain-to-brain interface supports information exchange for locomotion control
Chinese researchers established an optical BtBI that supports rapid information transmission for precise locomotion control, thus providing a proof-of-principle demonstration of fast BtBI for real-time behavioral control.

Transplanting human nerve cells into a mouse brain reveals how they wire into brain circuits
A team of researchers led by Pierre Vanderhaeghen and Vincent Bonin (VIB-KU Leuven, Université libre de Bruxelles and NERF) showed how human nerve cells can develop at their own pace, and form highly precise connections with the surrounding mouse brain cells.

Brain scans reveal how the human brain compensates when one hemisphere is removed
Researchers studying six adults who had one of their brain hemispheres removed during childhood to reduce epileptic seizures found that the remaining half of the brain formed unusually strong connections between different functional brain networks, which potentially help the body to function as if the brain were intact.

Alcohol byproduct contributes to brain chemistry changes in specific brain regions
Study of mouse models provides clear implications for new targets to treat alcohol use disorder and fetal alcohol syndrome.

Scientists predict the areas of the brain to stimulate transitions between different brain states
Using a computer model of the brain, Gustavo Deco, director of the Center for Brain and Cognition, and Josephine Cruzat, a member of his team, together with a group of international collaborators, have developed an innovative method published in Proceedings of the National Academy of Sciences on Sept.

Read More: Brain News and Brain Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.