Papel del receptor cb2 cannabinoide en la generación y supervivencia de células neurales en procesos neurodegenerativos

Resumen

The endocannabinoid system regulates the functionality of many synapses by inhibiting neurotransmitter release via presynaptic CB1 cannabinoid receptors and is also known to be involved in the regulation of neural cell fate. Thus, CB1 cannabinoid rec eptors are neuroprotective in different models of brain injury, as well as in neuroinflammatory conditions and neurodegenerative diseases. Recent findings have demonstrated the presence of a functional endocannabinoid system that participates in the regulation of neural progenitor cell proliferation and differentiation thought CB1 cannabinoid receptors. This Thesis provides evidence that CB2 cannabinoid receptors control neural cell generation and survival in several neurodegenerative situati ons. Specifically, CB2 cannabinoid receptors are shown to participate in the control of neural progenitor cell proliferation in vitro and in vivo in the dentate gyrus of the hippocampus, under physiological and excitotoxic conditions. This Thesis als o demonstrates the involvement of CB2 cannabinoid receptors in neural cell survival by the control of neuroinflammation. Thus, their activation promotes neuroprotection in an animal model of multiple sclerosis by preventing lymphocyte infiltration, m icroglial activation and bone marrow-derived myeloid progenitor cell recruitment into the inflammed CNS. Morover, CB2 cannabinoid receptors prevent striatal neurodegeneration in animal models of Huntington¿s disease by controlling microglial activati on. All these results support the potential of CB2 cannabinoid receptor agonists as therapeutic targets in the management of neurodegenerative and neuroinflammatory disorders.