Buckley NE, Hansson S, Harta G, Mezey E. Expression of the CB1 and CB2 receptor messenger RNAs during embryonic development in the rat. Neuroscience 82: 1131-1149
ABSTRACT We mapped the distribution of CB1 and CB2 receptor messenger RNAs in the developing rat to gain insight into how cannabinoids may affect embryogenesis. In situ hybridization histochemistry studies were done using riboprobes specific for CB1 or CB2 receptor messenger RNAs. We found that CB1 and CB2 receptor messenger RNAs are expressed in the placental cone and in the smooth muscle of the maternal uterus at the earliest gestational periods studied [from eight days of gestation (E8) through E12]. In the embryo, as early as E11, CB1 receptor messenger RNA is expressed in some cells of the neural tube and, at later embryological stages (from E15 to E21), in several distinct structures within the central nervous system. In addition, high levels of CB1 receptor messenger RNA were also found in areas of the peripheral nervous system such as the sympathetic and parasympathetic ganglia, in the retina and in the enteric ganglia of the gastrointestinal tract. In addition to neural structures, high levels of the CB1 receptor messenger RNA were also present in two endocrine organs, the thyroid gland and the adrenal gland. On the other hand, CB2 receptor messenger RNA is expressed exclusively in the liver of the embryo as early as E13. The region-specific expression of CB1 and CB2 receptor messenger RNAs suggests that these receptors have a functional role during embryogenesis.
Full-textDOI: · Available from: Stefan R Hansson, Sep 26, 2015
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- "The functional role of CB receptors in NSCs has been studied through the administration of selective receptor agonists and receptors activators which lead to NSCs proliferation and neurosphere formation in both embryonic and adult brain    . In particular, it has been shown that CB2 receptors mediate NSCs proliferation in an age-dependent manner, suggesting that CB2 selective activation could restore proliferative capacity of SVZ cells  which normally declined with age . "
ABSTRACT: Neural stem cells (NSCs) are self-renewing cells that can differentiate into multiple neural lineages and repopulate regions of the brain after injury. Mesenchymal stem cells (MSCs) are multipotent stromal cells that could differentiate into a variety of cell types, including neuronal cells. Recently, repair of human central nervous system (CNS) has become a therapeutic approach that is under preclinical investigation for CNS neurodegenerative disorders (CNSnd). However, CNSnd differ in the types and groups of cells involved and in the clinical manifestations. Consequently, the cells used for the potential cellular therapies will depend upon the affected cell population. Theoretically, NSCs and MSCs have the potential to produce all cell types of the CNS under specific stimuli, but the molecular targets governing the maturation and the differentiation of specific neuronal populations are not yet well identified. Cannabinoids (CBs) by cannabinoid receptors (CB1 and CB2) and by CB related receptors as Peroxisome proliferator-activated receptor gamma (PPAR-γ) Transient Receptor Potential Vanilloid type 1 (TRPV1) and type 2 (TRPV2), were found to modulate neuronal functions including neurogenesis. The aim of this review is to highlight recent researches regarding CB receptors and CB related receptors, in the regulation of NSCs differentiation and their potential use in CNSnd stem cell-based therapies.Frontiers in Clinical Drug Research -CNS and Neurological Disorders, Bentham edited by Atta-ur-Rahman, 07/2015: chapter Potential Roles of Cannabinoids in Cell Therapy for CNS Neurodegenerative Disorders: pages 3-18; , ISBN: 978-1-60805-927-0
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- "The endocannabinoid system is critical for neurodevelopment and as such is present in early development, and maintains expression throughout life (Figure 2B), exhibiting a broad spatial distribution to regulate synaptic plasticity (10, 11). The CB1R is found in numerous central nervous system structures as early as the eleventh embryonic day, and throughout the embryonic period this receptor is expressed in subcortical and cortical regions (12). In cortical projection neurons, CB1R and local eCBs facilitate the fasciculation of descending efferents and thalamic afferents, orchestrating the tight coupling of these two tracts (13). "
ABSTRACT: Cannabis use is increasingly pervasive among adolescents today, even more common than cigarette smoking. The evolving policy surrounding the legalization of cannabis reaffirms the need to understand the relationship between cannabis exposure early in life and psychiatric illnesses. cannabis contains psychoactive components, notably Δ(9)-tetrahydrocannabinol (THC), that interfere with the brain's endogenous endocannabinoid system, which is critically involved in both pre- and post-natal neurodevelopment. Consequently, THC and related compounds could potentially usurp normal adolescent neurodevelopment, shifting the brain's developmental trajectory toward a disease-vulnerable state, predisposing early cannabis users to motivational, affective, and psychotic disorders. Numerous human studies, including prospective longitudinal studies, demonstrate that early cannabis use is associated with major depressive disorder and drug addiction. A strong association between schizophrenia and cannabis use is also apparent, especially when considering genetic factors that interact with this environmental exposure. These human studies set a foundation for carefully controlled animal studies which demonstrate similar patterns following early cannabinoid exposure. Given the vulnerable nature of adolescent neurodevelopment and the persistent changes that follow early cannabis exposure, the experimental findings outlined should be carefully considered by policymakers. In order to fully address the growing issues of psychiatric illnesses and to ensure a healthy future, measures should be taken to reduce cannabis use among teens.Frontiers in Psychiatry 10/2013; 4:129. DOI:10.3389/fpsyt.2013.00129
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- "Emerging evidence suggests that CB 2 agonists are analgesic in a number of neuropathic, inflammatory pain and postoperative pain models (Ibrahim et al., 2003; Nackley et al., 2003; Hohmann et al., 2004; LaBuda et al., 2005). However, there is little evidence for CB 2 R expression in normal spinal cord (Buckley et al., 1998). CB 2 R expression is induced in the spinal cord, following nerve injury and the development of a neuropathic state and postoperative pain (Zhang et al., 2003; LaBuda et al., 2005). "
ABSTRACT: The present study was undertaken to investigate the relative contribution of cannabinoid receptors (CBRs) subtypes and to analyze cannabimimetic mechanisms involved on the inhibition of AEA and 2-AG degradation on the antihyperalgesic effect of ankle joint mobilization (AJM). Mice (25-35g) were subjected to plantar incision (PI) and 24 hours after surgery animals received the following treatments, AJM for 9 minutes, anandamide (10 mg/kg, intraperitoneal [i.p.]), WIN 55,212-2 (1.5 mg/kg, i.p.), URB937 (0.01-1 mg/kg, i.p.; a fatty acid amide hydrolase [FAAH] inhibitor) or JZL184 (0.016-16 mg/kg, i.p.; a monoacylglycerol lipase [MAGL] inhibitor). Withdrawal frequency to mechanical stimuli was assessed 24 hours after PI and at different time intervals after treatments. Receptor specificity was investigated using selective CB1R (AM281) and CB2R (AM630) antagonists. In addition, the effect of the FAAH and MAGL inhibitors on the antihyperalgesic action of AJM was investigated. AJM, anandamide, WIN 55,212-2, URB937 and JZL184 decreased mechanical hyperalgesia induced by PI. The antihyperalgesic effect of AJM was reversed by pretreatment with AM281 given by intraperitoneal and intrathecal routes, but not intraplantarly. Additionally, intraperitoneal and intraplantar, but not intrathecal administration of AM630 blocked AJM-induced antihyperalgesia. Interestingly, in mice pretreated with FAAH or the MAGL inhibitor the antihyperalgesic effect of AJM was significantly longer. This article presents data addressing the cannabinoid receptor mechanisms underlying the antihyperalgesic activity of joint mobilization as well as of the endocannabinoid catabolic enzyme inhibitors in the mouse postoperative pain model. Joint mobilization and these enzymes offer potential targets to treat postoperative pain.Neuroscience 10/2013; 255. DOI:10.1016/j.neuroscience.2013.09.055 · 3.36 Impact Factor