Endocannabinoids and the brain immune system: new neurones at the horizon?

Whereas, in most brain compartments, neuronal cell renewal during early life is replaced by synaptic plasticity and the potentiation of existing pathways and connections, neurogenesis in the hippocampus occurs throughout adulthood. Neuronal progenitor cells in the dentate gyrus of the hippocampus are thought to be the gatekeepers of memory. Neural progenitor cell proliferation and differentiation depends on their intrinsic properties and local environment and is down-regulated in conditions associated with brain inflammation. Conversely, newly-formed neurones can survive despite chronic inflammation and, moreover, specifically arise within an inflammatory environment. Since the endocannabinoid system controls immune responses via multiple cellular and molecular targets and influences cell proliferation, fate decision and cell survival in the central nervous system, we summarise how neurogenesis might be regulated by brain cannabinoids, either directly or indirectly via the immune system. This review presents clear evidence that the cannabinoid system influences adult neurogenesis. However, there is considerable variability with regard to the strain, model and methods utilised and therefore it is difficult to compare studies investigating the cannabinoid system. As a result, it remains far from clear exactly how endocannabinoids regulate neurogenesis.