Pedro Grandes: Current research on the endocannabinoid sytem

Dr. Pedro Grandes is visiting UVIC on sabbatical from the University of the Basque Country where he is a Professor in the Department of neurosciences. He is here to expand his research on the endocannabinoid system and share his expertise in brain imaging techniques. Read about his exciting research below. 

Dr. Pedro Grandes

The endocannabinoid (eCB) system is a complex endogenous signalling system that participates in multiple metabolic pathways. The cannabinoid CB1 receptor of this system is the most abundant G-protein coupled receptor in the brain and is involved in many brain functions ranging from food intake to cognition, through the modulation of synaptic transmission and plasticity. Also, the CB1 receptor is the target of (−)-trans-Δ9-tetrahydrocannabinol (THC), the main psychoactive compound of the Cannabis plants, and the alteration of the eCB system participates in the pathogenesis of multiple neurological and neuropsychiatric disorders. The CB1 receptor is highly expressed on inhibitory GABAergic synaptic terminals, and at low levels in other cellular and subcellular compartments where it plays very important functional roles. For instance, the activation of the scarce CB1 receptors expressed in astrocytes promotes astroglial differentiation and regulates synaptic transmission and plasticity through the modulation of neuron-astrocyte crosstalk. Astroglial CB1 receptors activation by acute cannabinoids impairs working memory; also, CB1 receptors in astrocytes control the leptin receptor expression in cultured cortical and hypothalamic astrocytes needed for energy supply to the brain.

Our main research interest is to investigate the anatomical localization as well as the functional and pathophysiological significance of the low CB1 receptor expression in glial cells of the rodent brain. This is important to know because the astroglial function in healthy and diseased brain depends on the structural relationship established by the astroglial processes with neuronal compartments, particularly at the synapses where the neurotransmitters are released and have access to the astroglial receptors.

Our efforts are specifically concentrated to decipher how the CB1 receptors are distributed within astroglial as well as other glial cell types with respect to the surrounding excitatory and inhibitory synapses. We are also devoted to study theCB1 receptor distribution in astrocytes of the adult brain under pathological states, such as epilepsy and after THC or ethanol exposure during adolescence.  We use advanced brain imaging techniques based on fluorescence and high resolution electron microscopy for studying the precise subcellular, synaptic and subsynaptic localization of the CB1 receptors and other receptor proteins at the brain cells and networks. 

READ: Read one of Dr. Grandes' most recent publications:  Gutiérrez-Rodríguez, A., Puente, N., Elezgarai, I., Ruehle, S., Lutz, B., Reguero, L., Gerrikagoitia, I., Marsicano, G. and Grandes, P. (2017), Anatomical characterization of the cannabinoid CB1 receptor in cell-type–specific mutant mouse rescue models. J. Comp. Neurol., 525: 302–318. doi:10.1002/cne.24066