The Pro-neurogenic Effects of Cannabidiol and Its Potential Therapeutic Implications in Psychiatric Disorders.

Figure 1

The pro-neurogenic effects of cannabidiol (CBD) and its functional relevance. (A) Adult hippocampal neurogenesis originates from type 1 precursor cells that might differentiate into granule neurons (Kriegstein and Alvarez-Buylla, 2009). The newly generated cells can be stimulated via GABAergic, endocannabinoid- and serotonin-dependent mechanisms (Encinas et al., ; Prenderville et al., 2015). The proliferation phase ends just after precursor cells exit the cell cycle. As early as 1 day after such an event, newborn neurons start expressing the postmitotic marker NeuN, which then declines as most newborn cells are eliminated before they become functional (survival phase; Kempermann et al., 2015). Within days after generation, newborn neurons send their axons to cornu ammonis 3 (CA3), where they form proper synapses (Sun et al., 2013). In the next phase, newborn neurons mature as the excitatory nature of GABA inputs shift into the standard depolarizing profile. Finally, new mature neurons go through a phase of increased synaptic plasticity, which in turn promotes its final integration into the hippocampal circuitry (functional integration phase; Ge et al., 2007). The effects of CBD are preferentially focused on the post-mitotic stages of the neurogenic process, whenever it facilitates neuronal maturation and impedes early neuronal death. (B) The pro-neurogenic effects of CBD are orchestrated by the eCB system. Furthermore, CBD upregulates different molecular components of downstream pathways usually associated with the eCB-driven facilitation of adult neurogenesis. Final molecular effectors of the protein synthesis and survival machinery of the hippocampus such as brain-derived neurotrophic factor (BDNF), calbindin, MAP-2, synapsin 1, and the activation of protective peroxisome proliferator-activated gamma (PPARγ) receptors, are also found upregulated after CBD subchronic treatments. (C) The figure represents a simplified vision of the hippocampal neurocircuitry functionally coupled to the neurogenic state of the dentate gyrus (DG). The hippocampus (ventral part) sends direct projections to the GABAergic interneurons of the BNST that, in turn, tune-down the hypothalamus–pituitary–adrenal (HPA) axis (Snyder et al., 2011). Direct projections from the hippocampus to the mPFC promote stress sensitivity (Padilla-Coreano et al., 2016), and mediate antidepressant effects (Bagot et al., 2015). Ventral hippocampal outputs to the BLA are involved in the feedforward inhibition of fear and anxiety-related responses (Bazelot et al., 2015). Finally, the hippocampus can indirectly influence VTA DA release in motivated tasks by activating medium spiny neurons of the NAc (Britt et al., 2012). Abbreviations: GFAP, glial fibrillary acidic protein; Mol, molecular layer; GCL, granule cell layer; AEA, anandamide; mPFC, medial prefrontal cortex; NAc, nucleus accumbens; BLA, basolateral amygdala; BNST, bed nucleus of the stria terminalis; VTA, ventral tegmental area. Created with Biorender.com.

L’article The Pro-neurogenic Effects of Cannabidiol and Its Potential Therapeutic Implications in Psychiatric Disorders. est apparu en premier sur Cannabis Belgique.

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