Project Details
Projekt
Function of the endocannabinoid system in normal and pathological ageing processes of the brain
Subject Area
Biological Psychiatry
Term
from 2008 to 2016
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 42860621
We have shown previously that there is an increased neuroinflammation in the brain of animals lacking CB1 receptors on GABAergic neurons. This highly unexpected result led us to the hypotheses that (1) CB1 receptor activity is important for the communication between GABAergic neurons and glial cells and (2) CB1 receptor activity on GABAergic neurons is protective against age-related neuroinflammatory changes. Therefore we ask, how modulation of CB1 receptor activity influences neuron-glia cross talk. Our previous results also suggested that CB1 receptor activity influences neuronal survival and apoptosis. In order to identify the mechanisms, by which chronic increase or cessation of CB1 receptor activity influences neuronal fate, we will investigate how the AKT and ERK signaling pathway is altered in the brain after chronic blockade or elevation of CB1 receptor activity. Finally, we reported that a lack of CB1 receptor activity leads to exacerbated cellular stress and neuroinflammation in the hippocampus, accompanied by early onset of cognitive deficits. We now ask whether an enhanced CB1 receptor activity induced by genetic or pharmacological blockade of the endocannabinoid degrading enzyme monoacylglycerol lipase (MAGL) or fatty acid amide hydrolase (FAAH) is beneficial against age-related changes in the brain. As a compensatory mechanism, however, the chronic elevation of endocannabinoid levels may lead to a decrease in CB1 receptor density. Therefore, we will first identify a pharmacological treatment regime leading to a sustained elevation in CB1 receptor activity.
DFG Programme
Research Units
