CONICET | Buscador de Institutos y Recursos Humanos

Cannabinoid receptors are expressed in the hippocampus. CB1R is preferentially expressed in pyramidal neurons and astrocytic processes, while CB2R is expressed in microglial, astroglial and endothelial cells. CB1-receptor-knockout mice are used as an animal model of depression, although the morphological substrate of this behavior is not completely understood yet.And, as the hippocampus is an important area of the central nervous system involved in behavior, the aim of this work was to characterize hippocampal neurons in CB1-receptor-knockout mice.The study was performed through immuno􀀺uorescence, Golgi, Western blot and electron microscopy techniques, focusing on the dentate gyrus and CA1 areas.The genetic ablation of CB1R produces an increase in the expression of CB2R, which suggests a compensatory regulation in the endocannabinoid system.CB1-receptor-knockout mice evidenced a lower number of undi􀀾erentiated neuronal cells precursors (Nestin+ cells) and migrating neuroblasts (doublecortin+cells). These data suggest that CB1-receptor-knockout mice su􀀾er alterations in adult neurogenesis in the in dentate gyrus.CB1-receptor-knockout mice also presented cytoskeletal alterations in hippocampal neurons, as evidenced by lower expression of Neuro􀁀laments of 160Kda and 200Kda, as well as lower expression of MAP-2 protein. These results indicate that these neurons have scarce dendritic arborization and cannot correctly connect with their targets neurons.The number of synaptic contacts studied by Golgi technique and electron microscopy did not show signi􀁀cant di􀀾erences between CB1-receptor-knockout mice and wild type mice; however, synaptophysin expression was lower in CB1-receptor-knockout mice, probably suggesting alterations in synapse e􀁂ciency.Taken together, these results could explain the behavior alterations in CB1-receptor-knockout mice.