Cannabinoids modulate Olig2 and polysialylated neural cell adhesion molecule expression in the subventricular zone of post‐natal rats through cannabinoid receptor 1 and cannabinoid receptor 2

Abstract

The subventricular zone (SVZ) is a source of post‐natal glial precursors that can migrate to the overlying white matter, where they may differentiate into oligodendrocytes. We showed that, in the post‐natal SVZ ependymocytes, radial glia and astrocyte‐like cells express cannabinoid receptor 1 (CB1), whereas cannabinoid receptor 2 (CB2) is found in cells expressing the polysialylated neural cell adhesion molecule. To study CB1 and CB2 function, post‐natal rats were exposed to selective CB1 or CB2 agonists (arachidonyl‐2‐chloroethylamide and JWH‐056, respectively) for 15 days. Accordingly, we found that CB1 activation increases the number of Olig2‐positive cells in the dorsolateral SVZ, whereas CB2 activation increases polysialylated neural cell adhesion molecule expression in this region. As intense myelination occurs during the first weeks of post‐natal development, we examined how modulating these factors affected the expression of myelin basic protein. Pharmacological administration of agonists and antagonists of CB1 and CB2 showed that the activation of both receptors is needed to augment the expression of myelin basic protein in the subcortical white matter.

CB2 Cannabinoid Receptors Promote Neural Progenitor Cell Proliferation via mTORC1 Signaling

“…On the other hand, CB 1 receptors exert a proapoptotic action on transformed glial cells via Akt/mTORC1 inhibition (36). In addition, oligodendrocyte progenitor survival and differentiation is regulated by CB 1 receptors via PI3K/Akt signaling (9) and cannabinoid agonists induce myelin basic protein expression and myelination during postnatal development (37) in a process that is blocked in vitro by rapamycin (38). This suggests a role of CB 1 receptor-mediated PI3K/Akt/mTORC1 signaling in oligodendroglial cells, which is in agreement with the role of Rheb1-mediated activation of mTORC1 in myelination and oligodendrocyte differentiation (39).…”

Endocannabinoids via CB1receptors act as neurogenic niche cues during cortical development

“…The involvement of the CB 1 receptor in embryonic neuronal development [85], but also in postnatal astrogliogenesis [27] and oligodendrocyte survival and myelination [80,86], suggests that CB 1 receptor signalling could also target still unknown pro-gliogenic transcription factors [3]. ECB signalling may be involved in tumour-initiating stem cell decisions of proliferation versus cell cycle exit and differentiation [87], and CB 1 receptor regulation of STAT3 is a likely candidate to mediate CBI regulation of astrogliogenesis [88].…”

“…The neurobiological consequences of plant-derived cannabinoid intake on pre-and postnatal stages have been recently reviewed from the perspective of animal models and humans [6,93], and indicate that the brain burst period is of especial susceptibility. According to the developmental stage in which CB 1 receptor signalling is functional, its interference may affect different neural cell populations, including neuronal generation and specification (embryonic stages) [13,37], glial development (postnatal stages) [27,80] and neuronal maturation and connectivity [13,32,94]. Blockade of the CB 1 receptor when the neurogenic wave responsible for deep cortical neuronal generation is active affects corticospinal neuronal specification, thereby tuning subcerebralversus callosal neuron-projections and thus skilled motor function in adulthood [83].…”

Patterns of Brain Structural Changes in First-Contact, Antipsychotic Drug-Naïve Patients with Schizophrenia

“…All of these findings are compatible with the ability of the cannabinoid receptor stimulation to increase the oligodendrocyte transcription factor Olig2 as well as the expression of myelin basic protein. 44 Some technical limitations of this study also need to be considered. The diffusion tensor model is currently the framework most commonly used to relate the diffusion signal to the direction of the fibers.…”