Science：小鼠研究揭示大麻可能打乱大脑发育的线索

The temporal and spatial coincidence of CB₁R localization with endocannabinoid availability during corticogenesis. (A) Schemes of the telencephalon at the embryonic days indicated. Colored symbols refer to particular structures in adjoining photomicrographs. At E14.5 to 16.5 (fig. S2B), CB₁R mRNA is preferentially expressed in pyramidal cells of the hippocampus (B) and cerebral cortex (C), with CB₁R immunoreactivity localized to developing long-range axons, coexpressing growth-associated protein 43 (GAP43), in the intermediate zone (9) (D and E). (F) CB₁R processes, axons emitted by pyramidal neurons, in the fimbria. A three-dimensional reconstruction of a process is depicted in a semitransparent manner. A dotted line encircles the individual profile (1) shown to the right. (2) Adjacent CB₁R processes (dotted line) with 3,3'-diaminobenzidine (DAB)–Ni reaction end products (black) precipitating on the inner plasmalemmal surface (arrows) after the use of an antibody recognizing the C terminus of CB₁R. (G) Hippocampal interneurons (arrows) express CB₁R mRNA at E18.5. (H) At birth, CB₁Rs are spatially associated with GABAergic axons (arrows) navigating locally in the hippocampus. (I) Reciprocally perpendicular projections of a single CB₁R growth cone from the hilus of newborn rat hippocampus. Numbers indicate the positions of planar images. Arrowheads indicate the truncated axon. DAB precipitation fills the cytoplasm, which also contains numerous vesicles (arrows). (J) CB₁Rs concentrate in growth cone particles (GCPs) relative to total cortical lysates, as shown by Western analysis. (K) DAGL predominates in the neocortex at birth and (L) is expressed by pyramidal cells. Arrows point to gold particles indicating the precise subcellular localization of DAGL . (M) Similarly, DAGL