AUTHOR=Manterola Andrea , Chara Juan Carlos , Aguado Tania , Palazuelos Javier , Matute Carlos , Mato Susana 

TITLE=Cannabinoid CB1 receptor expression in oligodendrocyte progenitors of the hippocampus revealed by the NG2-EYFP-knockin mouse

JOURNAL=Frontiers in Neuroanatomy

VOLUME=16

YEAR=2022

URL=https://www.frontiersin.org/journals/neuroanatomy/articles/10.3389/fnana.2022.1030060

DOI=10.3389/fnana.2022.1030060

ISSN=1662-5129

ABSTRACT=<p>Adult oligodendrocyte progenitor cells (OPCs) give rise to myelinating oligodendrocytes through life and play crucial roles in brain homeostasis and plasticity during health and disease. Cannabinoid compounds acting through CB<sub>1</sub> receptors promote the proliferation and differentiation of OPCs <italic>in vitro</italic> and facilitate developmental myelination and myelin repair <italic>in vivo</italic>. However, CB<sub>1</sub> receptor expression in adult OPCs <italic>in situ</italic> has not been corroborated by anatomical studies and the contribution of this receptor population to the (re)myelination effects of cannabinoids remains a matter of debate. Using electron microscopy methods applied to NG2-EYFP reporter mice we assessed the localization of CB<sub>1</sub> receptors in OPCs of the adult mouse hippocampus. To control for the specificity of CB<sub>1</sub> receptor immunostaining we generated transgenic mice bearing EYFP expression in NG2 glia and wild-type (NG2-EYFP-CB<sub>1</sub><sup>+/+</sup>) and knockout (NG2-EYFP-CB<sub>1</sub><sup>–/–</sup>) for CB<sub>1</sub> receptors. Double immunogold and immunoperoxidase labeling for CB<sub>1</sub> and EYFP, respectively, revealed that CB<sub>1</sub> receptors are present in a low proportion of NG2 positive profiles within hippocampal s<italic>tratum radiatum</italic> of NG2-EYFP-CB<sub>1</sub><sup>+/+</sup> mice. Quantitative analysis of immunogold particles in synaptic structures and NG2 profiles showed that CB<sub>1</sub> receptors are expressed at lower density in adult OPCs than in glutamatergic cells of the rodent hippocampus. These results highlight the presence of CB<sub>1</sub> receptors in adult OPCs thus providing an anatomical substrate for the remyelination promoting effects of cannabinoids and open a novel perspective on the roles of the endocannabinoid system in brain physiology through the modulation of NG2 glia.</p>