HCAR1/GPR81 action on inflammation investigated in RFP reporter mice and knock-out mice
Physical activity has positive effects on brain functions and especially on aging brains, but the initial signals that start these positive effects remain to be explored. The lactate receptor, G-protein-coupled receptor 81 (GPR81), also known as hydroxycarboxylic acid receptor 1 (HCA1 or HCAR1), has been identified in mammalian brain by our group (Lauritzen KH et al 2014 Cereb Cortex; Morland C et al 2015 J Neurochem Res). Recent findings suggest crucial roles of GPR81 in brain, linking exercise and brain function (Morland C et al 2017 Nat Commun). We want to examine mice expressing red fluorescent protein (RFP) under the GPR81 promoter in order to demonstrate changes in RFP expression in the brain as an indicator (tag) of GPR81, as well as the effects of GPR81 agonists in wild-type (wt) and knockout (ko) mice (Ahmed K et al 2010 Cell Metab). In previous experiments (ID6720 and ID8243) we found these mice to be suitable. The mice are bred in the Department (ID12521).
In the present pilot project, we focus on short term activation of GPR81, which has shown dramatic beneficial effects against inflammatory tissue damage in peripheral organs (Hoque R et al 2014 Gastroenterology; Madaan A et al 2017 Am J Obstet Gynecol), but has never been tested for such effects in the CNS. Inflammatory tissue damage is recently recognized as contributing improtanly to neurodegenerative disease such as Alzheimer's (Pennisi M et al 2017 J Neurosci Res).
The research is expected to contribute to improved understanding of how physical activity benefits the brain, including in age-related diseases such as diabetes and dementias, and thereby to finding therapeutic use of the mechanisms involved. We plan to use 360 mice (Mus musculus) in the experiments. No adverse effects on well-being (pain, distress) are expected. The working team is well trained and able to successfully perform animal research. Ethical concerns will be fully addressed according to law and civil regulations.
In the present pilot project, we focus on short term activation of GPR81, which has shown dramatic beneficial effects against inflammatory tissue damage in peripheral organs (Hoque R et al 2014 Gastroenterology; Madaan A et al 2017 Am J Obstet Gynecol), but has never been tested for such effects in the CNS. Inflammatory tissue damage is recently recognized as contributing improtanly to neurodegenerative disease such as Alzheimer's (Pennisi M et al 2017 J Neurosci Res).
The research is expected to contribute to improved understanding of how physical activity benefits the brain, including in age-related diseases such as diabetes and dementias, and thereby to finding therapeutic use of the mechanisms involved. We plan to use 360 mice (Mus musculus) in the experiments. No adverse effects on well-being (pain, distress) are expected. The working team is well trained and able to successfully perform animal research. Ethical concerns will be fully addressed according to law and civil regulations.