Chronic low-dose Delta(9)-tetrahydrocannabinol (THC) treatment stabilizes dendritic spines in 18-month-old mice

Cognitive functions decline during aging. This decline could be caused by changes in dendritic spine stability and altered spine dynamics. Previously, we have shown that a low dose chronic THC treatment improves learning abilities in old whereas impairs learning abilities in young mice. The mechanism underlying this age-dependent effect is not known. Dendritic spine stability is a key for memory formation, therefore we hypothesized that THC affects spine dynamics in an age-dependent manner. We applied longitudinal 2-photon in vivo imaging to 3- and 18-month-old mice treated with 3 mg/kg/day of THC for 28 days via an osmotic pump. We imaged the same dendritic segments before, during and after the treatment and assessed changes in spine density and stability. We now show that in old mice THC improved spine stability resulting in a long-lasting increase in spine density. In contrast, in young mice THC transiently increased spine turnover and destabilized the spines.

Automated summary

Cognitive function declines with age, possibly due to changes in dendritic spine stability and dynamics. Previous studies have shown that chronic low-dose THC treatment improves learning abilities in old mice, but impairs learning abilities in young mice. The underlying mechanism for this age-dependent effect is unclear. In this study, we used longitudinal 2-photon in vivo imaging to investigate how THC affects dendritic spine density and stability in 3- and 18-month-old mice. We found that THC improved spine stability and increased spine density in old mice, while transiently increasing spine turnover and destabilizing spines in young mice.