Role of cannabinoid system in systemic and brain ageing
Final Report Abstract
Mice with constitutive or conditional deletion of the cannabinoid receptor type 1 (CB1) showed accelerated brain ageing and early onset of several symptoms of physical ageing. Increased CB1 receptor activity improved learning and memory functions, and restored synapse density and gene expression profiles in the brains of old individuals to those of young individuals. All these findings suggest that the activity of the cannabinoid system influences the ageing process. However, it was not known whether CB1 receptor activity exerts its anti-aging effect locally or systematically. Our present work has shown that animals with hippocampus-specific deletion have a similar memory deficit and neuroinflammation as the conditional knockout animals. Hypothalamus-specific deletion of CB1 receptors led to neuroinflammation and impaired insulin-like growth factor signalling in the hypothalamus without histological evidence of altered physical ageing. These results now show that 1. local CB1 receptor activity is responsible for regulating glial inflammatory activity and thus ageing in the brain. 2. Hypothalamic CB1 receptor activity and the resulting neuroinflammation per se do not significantly influence physical ageing. Finally, we reported that chronic lowdose treatment with tetrahydrocannabinol alone was more effective in improving learning in aged mice than the 1:1 combination of tetrahydrocannabinol and cannabidiol. This finding is important for the design of clinical trials to test the antiageing effects of cannabis derivatives.
Publications
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Efficacy of Δ9 -Tetrahydrocannabinol (THC) Alone or in Combination With a 1:1 Ratio of Cannabidiol (CBD) in Reversing the Spatial Learning Deficits in Old Mice. Frontiers in Aging Neuroscience, 13.
Nidadavolu, Prakash; Bilkei-Gorzo, Andras; Krämer, Michael; Schürmann, Britta; Palmisano, Michela; Beins, Eva C.; Madea, Burkhard & Zimmer, Andreas
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Dynamic Changes in the Endocannabinoid System during the Aging Process: Focus on the Middle-Age Crisis. International Journal of Molecular Sciences, 23(18), 10254.
Nidadavolu, Prakash; Bilkei-Gorzo, Andras; Effah, Felix; Leidmaa, Este; Schürmann, Britta; Berger, Moritz; Bindila, Laura; Schmid, Matthias; Lutz, Beat; Zimmer, Andreas & Bailey, Alexis
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Hippocampal Deletion of CB1 Receptor Impairs Social Memory and Leads to Age-Related Changes in the Hippocampus of Adult Mice. International Journal of Molecular Sciences, 24(1), 26.
Palmisano, Michela; Gargano, Alessandra; Olabiyi, Bolanle Fatimat; Lutz, Beat & Bilkei-Gorzo, Andras
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Regulation of adult neurogenesis by the endocannabinoid-producing enzyme diacylglycerol lipase alpha (DAGLa). Scientific Reports, 12(1).
Schuele, Lena-Louise; Schuermann, Britta; Bilkei-Gorzo, Andras; Gorgzadeh, Sara; Zimmer, Andreas & Leidmaa, Este
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Possible role of locus coeruleus neuronal loss in age-related memory and attention deficits. Frontiers in Neuroscience, 17.
Gargano, Alessandra; Olabiyi, Bolanle Fatimat; Palmisano, Michela; Zimmer, Andreas & Bilkei-Gorzo, Andras
