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Miswiring the brain: Δ9-tetrahydrocannabinol disrupts cortical development by inducing an SCG10/stathmin-2 degradation pathway

Children exposed in utero to cannabis present permanent neurobehavioral and cognitive impairments. Psychoactive constituents from Cannabis spp., particularly Δ(9)-tetrahydrocannabinol (THC), bind to cannabinoid receptors in the fetal brain. However, it is unknown whether THC can trigger a cannabinoid receptor-driven molecular cascade to disrupt neuronal specification. Here, we show that repeated THC exposure disrupts endocannabinoid signaling, particularly the temporal dynamics of CB1…

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Figure 7. Δ9-tetrahydrocannabinol (THC) promotes ectopic filopodiagenesis

A,A2 Transient transfection of cortical neurons with a phospho-mimetic EGFP-SCG10S62D/S73D mutant (SCG10-DD) (Westerlund et al, 2011) led to a decrease in the primary neurite length, an effect equivalent to that of THC. SCG10-DD overexpression, which largely outcompeted endogenous SCG10 (insets), rendered THC ineffective to modify neurite elongation (> 15 neurons/condition). Western analysis demonstrated a progressive increase in SCG10-DD protein expression in PC12 cells upon transient transfection(A2). Probing by an anti-GFP antibody differentiated endogenous SCG10 from overexpressed SCG10-DD. Note that SCG10-DD overexpression significantly reduced the endogenous SCG10 content (wild-type (WT) targets around ˜20 kDa). Membranes were stained with amido-back to control for equal protein loading. B–B2 siRNA knockdown of SCG10 expression phenocopied and blunted the effects of THC on neurite outgrowth in cultured cortical neurons (> 20 neurons/condition). C SCG10 levels decreased in cortical growth cone particles exposed to THC for 10 min. SCG10 isoforms were numbered (Shin et al, 2012). Gapdh served as a loading control. D, D1 In cultured cortical neurons, THC (10 min) allowed acetylated tubulin accumulation (arrowheads) and the formation of superfluous lamellipodium-like F-actin-rich cytoskeletal projections. Bar histograms of quantitative subcellular morphometry are shown in (D2). THC facilitated the morphological differentiation of growth cones (D3) including filopodiogenesis (> 10 observations/condition; D4) without affecting the size of individual growth cones (D5). Growth cone morphology was classified as described by (Morii et al, 2006). E, E1 Besides affecting the growth cone, THC acutely increased the formation and density of F-actin+ axial protrusions, likely filopodia, from distal neurite shafts. Data information: Data were expressed as means ± s.e.m. **< 0.01, *< 0.05; n.s. = non-significant. Scale bars, 20 μm (A), 10 μm (B, D,D1,E)

Source: https://pubmed.ncbi.nlm.nih.gov/24469251/?utm_source=no_user_agent&utm_medium=rss&utm_campaign=pubmed-2&utm_content=1z7zlNEMzQex5jriqkhCblNtckSEpT9xYlxxeymU_73UTETESY&fc=20200804213258&ff=20200811100328&v=2.11.5

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Coinsmart. Beste Bitcoin-Börse in Europa
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Republished by Plato

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Coinsmart. Beste Bitcoin-Börse in Europa
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