Neuronal and synaptic morphological alterations in the hippocampus of cannabinoid receptor type 1 knockout mice

Abstract

Cannabinoid receptor type 1 (CB1R) modulates synaptic activity and is widely distributed in brain areas such as the hippocampus, cerebellum, cerebral cortex, and striatum, among others. CB1R is involved in processes such as memory, learning, motor coordination, and mood. Genetic deletion of CB1R causes behavioral alterations. In this work, we evaluated neuronal morphology and synaptic structure in the hippocampus of adult male CB1R knockout mice (CB1R−/−). Morphological changes in the CB1R−/− hippocampus evidenced a decrease in the expression of cytoskeletal proteins neurofilaments 160 KDa, neurofilaments 200 KDa, and microtubule-associated protein 2. CA1 neurons showed decreased arborization and changes in synaptic structure such as lower thickness of postsynaptic density and a reduction in synaptophysin levels. Results obtained in the present work provide evidence of the participation of CB1R in the establishment of neuronal structure and networks that could have an important role in neuronal plasticity. In addition, these changes observed in CB1R−/− could be correlated with behavioral alterations reported.