Endocannabinoid System As A Protector Of The Weak: CB1 Receptor Activity Influences Neurodegeneration In Locus Coeruleus

Alessandra Gargano1, Andras Bilkei-Gorzo1, Andreas Zimmer1


The endocannabinoid system (ECS) is an important neuromodulatory system that plays a crucial role in a large variety of homeostatic processes essential for maintaining the integrity of brain function. It has been shown that during ageing there is a decline of cognitive abilities and that this decline is influenced by the ECS: reduced endocannabinoid signaling leads to an early onset of learning and memory deficits associated with an age-related neuronal loss in the hippocampus. Our aim is to investigate the role of the ECS, especially of the CB1 receptor, in the Locus Coeruleus (LC), an area subject to age-related neurodegeneration in humans.

Our data show that in C57BL/6J mice there is a neuronal loss in LC comparable with findings in humans, and that the number of TH-positive cells starts declining in middle aged animals.

We didn’t find any difference when comparing the number of TH-positive cells in the LC of young wild-type and CB1ko animals. However, in old animals the number of noradrenergic neurons was significantly reduced in CB1ko mice, indicating a role of the CB1 receptor in LC integrity during ageing.

The density and morphology of microglia were altered in the CB1ko model, and a marker of mitophagy, pS65-ubiquitin, was likewise altered.

All together, our data suggest a neuroprotective function of the CB1 receptor in brain areas sensitive to age-related changes such as the LC. Further in vivo studies will investigate how these alterations in neuronal number influence the noradrenergic system and the ageing process.