Endocannabinoids via CB₁receptors act as neurogenic niche cues during cortical development

Abstract

During brain development, neurogenesis is precisely regulated by the concerted action of intrinsic factors and extracellular signalling systems that provide the necessary niche information to proliferating and differentiating cells. A number of recent studies have revealed a previously unknown role for the endocannabinoid (ECB) system in the control of embryonic neuronal development and maturation. Thus, the CB 1 cannabinoid receptor in concert with locally produced ECBs regulates neural progenitor (NP) proliferation, pyramidal specification and axonal navigation. In addition, subcellularly restricted ECB production acts as an axonal growth cone signal to regulate interneuron morphogenesis. These findings provide the rationale for understanding better the consequences of prenatal cannabinoid exposure, and emphasize a novel role of ECBs as neurogenic instructive cues involved in cortical development. In this review the implications of altered CB 1 -receptor-mediated signalling in developmental disorders and particularly in epileptogenesis are briefly discussed.

Morphine-induced locomotor sensitization produces structural plasticity in the mesocorticolimbic system dependent on CB1-R activity

“…These results reflect that disruption of chronic morphine treatment might be associated with a progressive waning of structural plasticity established in the NAc during morphine treatment. Similar results have also been described in dendrites of MSN of the NAc after prolonged withdrawal from a chronic cocaine treatment (Dumitriu et al, 2012). In contrast, disruption of chronic morphine treatment was associated with an increase in dendritic spine density, mainly thin spines, in the mPFC in both WT and CB1-R KO mice.…”

Prenatal exposure to cannabinoids evokes long-lasting functional alterations by targeting CB 1 receptors on developing cortical neurons

“…In agreement, early developmental exposure of chicken embryos to a THC analog (27) and genetic manipulation of the CB 1 R-interacting protein CRIP1 (28) have been shown to disrupt the appropriate balance of transcription factors that intrinsically drive neuronal development. Thus, CB 1 R signaling refines the molecular, laminar, and hodological identity of projection neurons in the pre-and postnatal cerebral cortex (5,6). The present findings support that THC can act as a functional suppressor of CB 1 R signaling, as restricted exposure to THC interferes with developmental CB 1 R function in a transient but functionally impacting manner.…”

“…The CB 1 R plays a pivotal neurodevelopmental role by transducing information from the endocannabinoid ligands present in the neurogenic niche into the coordination of the intrinsic developmental program of developing neurons (6,26). In agreement, early developmental exposure of chicken embryos to a THC analog (27) and genetic manipulation of the CB 1 R-interacting protein CRIP1 (28) have been shown to disrupt the appropriate balance of transcription factors that intrinsically drive neuronal development.…”

THC Treatment Alters Glutamate Receptor Gene Expression in Human Stem Cell-Derived Neurons

“…Although prenatal exposure is associated with negative effects on fetal brain development in humans [2,3,4,5,6,7,8,9], cannabis use is self-reported by over 25% of pregnant women [10]. The major psychoactive ingredient in cannabis is Δ9-tetrahydrocannabinol (THC), which acts primarily via the G-protein coupled cannabinoid receptor 1 (CB1R) [11], signaling via the activation of ERK kinases and/or the inhibition of adenyl cyclase (reviewed in [12,13]). …”