Longitudinal Imaging Of Cortical Dendritic Spines In Vivo During A Chronic Treatment With Low-dosage THC

Joanna Komorowska-Müller1, Kishore Aravind Ravichandran1, Anne-Kathrin Gellner2, Valentin Stein3, Andreas Zimmer1

1 Institute of Molecular Psychiatry, Medical Faculty, University of Bonn
2 Klinik und Poliklinik für Psychiatrie und Psychotherapie, Uniklinikum Bonn
3 Institute of Physiology II, Medical Faculty, University of Bonn

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The endocannabinoid system (ECS) is a lipid signalling system that modulates synaptic communication and other forms of cell-cell communication in the brain and in the periphery. Studies have proven that the ECS undergoes age-dependent changes, with an overall activity decrease in old individuals. We recently reported that a long-term treatment of old mice with a low-dosage of Δ9-tetrahydrocannabinol (THC), a cannabinoid receptor agonist, rejuvenates their gene expression patterns and improves their cognitive abilities to the level of young mice. These changes were accompanied by an increase in synapsin expression and spine numbers.

The purpose of this study was to evaluate the effects of THC administration on dendritic spine dynamics using in vivo imaging technique. We thus imaged the same dendritic segments in the somatosensory cortex in order to asses spine formation, stability and spine loss during and after the 28-days THC treatment in 3- and 18-month old mice for up to 10 weeks.

The analysis of the 18-month old cohort was challenging due to numerous technical difficulties associated with intracranial imaging of old mice. Nevertheless, we overcame the issues and efficiently imaged three cohorts which calculations are currently ongoing. Our results from the 3-month old cohort indicate that THC treatment did not alter the density of spines, but increased the turnover rate of spines during the first 2 weeks of treatment. In turn, it decreased the stability of both preexisting and newborn spines. This suggests that the THC treatment in young mice increased the dynamics of cortical dendritic spines.