Effects of Chronic Cannabis Smoke Exposure on Inflammatory Markers in Periphery and Brain in Young and Aged Mice

Abstract

Aging is associated with chronic low-grade inflammation, which is thought to contribute to both cognitive decline and various neurodegenerative diseases. Cannabinoids are reported to reduce levels of inflammatory markers; however, these effects have not been thoroughly assessed in aged subjects. To address this gap, we evaluated effects of chronic cannabis smoke exposure on peripheral and brain inflammatory markers in young and aged mice. Young adult (4 months old) and aged (22 months old) C57Bl/6J mice were exposed to smoke from burning either cannabis (5.5 - 6.2% THC) or placebo (0% THC) cigarettes daily for 30 consecutive days. Following exposure sessions, both blood and brain tissue from the prefrontal cortex (PFC) and hippocampus (HPC) were collected and analyzed for multiple markers of inflammation. Overall, the patterns of inflammatory markers varied across the three tissue types. Both comparisons of individual cytokines and global cytokine profiles revealed that aging caused modest increases in cytokine levels in serum and PFC, with little influence of cannabis exposure. In contrast, HPC samples had stronger age effects, with numerous cytokines elevated in aged mice compared to young. Cannabis also interacted with age in the HPC such that smoke exposure tended to increase cytokine levels in young mice but decrease them in aged mice. These findings point to general age-related increases in brain inflammatory markers in this mouse strain, but cannabis effects were largely restricted to the HPC, where smoke exposure produced age-dependent changes in cytokine profiles. HIGHLIGHTSO_LIAged C57BL/6 mice have elevated cytokines levels, especially in the hippocampus C_LIO_LICannabis smoke exposure produces age-dependent changes in cytokine levels in hippocampus C_LIO_LIIn HPC, cannabis smoke exposure attenuated age-related increases in IL-13 and Dkk1 C_LI