Abstract:
:The balance between detrimental, pro-aging, often stochastic processes and counteracting homeostatic mechanisms largely determines the progression of aging. There is substantial evidence suggesting that the endocannabinoid system (ECS) is part of the latter system because it modulates the physiological processes underlying aging. The activity of the ECS declines during aging, as CB1 receptor expression and coupling to G proteins are reduced in the brain tissues of older animals and the levels of the major endocannabinoid 2-arachidonoylglycerol (2-AG) are lower. However, a direct link between endocannabinoid tone and aging symptoms has not been demonstrated. Here we show that a low dose of Δ9-tetrahydrocannabinol (THC) reversed the age-related decline in cognitive performance of mice aged 12 and 18 months. This behavioral effect was accompanied by enhanced expression of synaptic marker proteins and increased hippocampal spine density. THC treatment restored hippocampal gene transcription patterns such that the expression profiles of THC-treated mice aged 12 months closely resembled those of THC-free animals aged 2 months. The transcriptional effects of THC were critically dependent on glutamatergic CB1 receptors and histone acetylation, as their inhibition blocked the beneficial effects of THC. Thus, restoration of CB1 signaling in old individuals could be an effective strategy to treat age-related cognitive impairments.
journal_name
Nat Medjournal_title
Nature medicineauthors
Bilkei-Gorzo A,Albayram O,Draffehn A,Michel K,Piyanova A,Oppenheimer H,Dvir-Ginzberg M,Rácz I,Ulas T,Imbeault S,Bab I,Schultze JL,Zimmer Adoi
10.1038/nm.4311subject
Has Abstractpub_date
2017-06-01 00:00:00pages
782-787issue
6eissn
1078-8956issn
1546-170Xpii
nm.4311journal_volume
23pub_type
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