[Andras Bilkei-Gorzo*: Institute of Molecular
Psychiatry, University of Bonn, Bonn 53127, Germany]
The role of endocannabinoids as
inhibitory retrograde transmitters is now widely known and intensively studied.
However, endocannabinoids also influence neuronal activity by exerting
neuroprotective effects and regulating glial responses. This review centres
around this less-studied area, focusing on the cellular and molecular
mechanisms underlying the protective effect of the cannabinoid system in brain
ageing. The progression of ageing is largely determined by the balance between
detrimental, pro-ageing, largely stochastic processes, and the activity of the
homeostatic defence system. Experimental evidence suggests that the cannabinoid
system is part of the latter system. Cannabinoids as regulators of
mitochondrial activity, as anti-oxidants and as modulators of clearance
processes protect neurons on the molecular level. On the cellular level, the
cannabinoid system regulates the expression of brain-derived neurotrophic
factor and neurogenesis. Neuroinflammatory processes contributing to the
progression of normal brain ageing and to the pathogenesis of neurodegenerative
diseases are suppressed by cannabinoids, suggesting that they may also
influence the ageing process on the system level. In good agreement with the
hypothesized beneficial role of cannabinoid system activity against brain
ageing, it was shown that animals lacking CB1 receptors show early onset of
learning deficits associated with age-related histological and molecular
changes. In preclinical models of neurodegenerative disorders, cannabinoids
show beneficial effects, but the clinical evidence regarding their efficacy as
therapeutic tools is either inconclusive or still missing.
Original Abstract: The endocannabinoid system in normal and pathological brain ageing
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