12/27/2023 0 Comments Pcb dendriteBut if the device does not break, creep corrosion will accumulate over time. Water ingress can cause the device to short out, killing the phone immediately. † p < 0.05 relative to PCB-95 alone.What people don’t realize is that simply drying out your phone is not a solution. ![]() * p < 0.05, and ** p < 0.01 relative to vehicle control. Transfection with the endogenous Wnt2 antagonist Wif blocked PCB-95 effects on dendritic length (–, without, +, with FLA365) ( F) and branching ( G) in 9-DIV hippocampal neurons co-transfected with MAP2B-EGFP (–, without, +, with Wif) (mean ± SE n = 30 neurons). ( E) PCB-95 increased Wnt2 mRNA in hippocampal neurons as determined by qPCR, and this effect was blocked by 10-µM FLA365 (mean ± SE n = 3 per condition). Expression of dnCREB or CREB shRNA inhibited PCB-95 effects on dendritic length ( C) and branching ( D) in 9-DIV hippocampal neurons co-transfected with MAP2B-EGFP (mean ± SE n = 30 neurons). ( B) Densitometry of blots probed for pCREB normalized to total CREB presented as percent of control (mean ± SE n = 3). ( A) Representative Western blot illustrating increased pCREB in hippocampal neurons (7 DIV) stimulated with BIC (20 µM, 30 min) or PCB-95 (200 nM). * p < 0.05 relative to vehicle control.ĬREB and Wnt2 activity are required for PCB-95–induced dendritic growth. Data are presented as mean ± SE ( n = 10–12 neurons from three independent dissections). Acute exposure to PCB-95 increased the frequency and amplitude of spontaneous Ca 2+ transients in soma and distal dendrites. Bar graphs at the right summarize Ca 2+ transient responses > 2× mean normalized to baseline fluorescence. ( C) 4CmC (100 µM) which activates RyR1 and RyR2, but not RyR3, was used to confirm the block of Ca 2+ channel activity. Neurons pretreated with ryanodine (500 µM, 1 hr) to block all RyR channel activity essentially negated the stimulatory actions of PCB-95 (lower two traces). ( B) Representative Ca 2+ transient activity captured from soma and distal dendrites of Fluo-4–loaded hippocampal neurons at 7 DIV before and after perfusion of PCB-95 (200 nM) (upper two traces). ![]() ( A) Representative Ca 2+ transient activity captured from soma and distal dendrites of Fluo-4–loaded hippocampal neurons at 7 DIV with perfusion of DMSO (0.01%) vehicle. Ryanodine blocks amplification of spontaneous Ca 2+ oscillations triggered by acute PCB-95 exposure. Our findings identify PCBs as candidate environmental risk factors for neurodevelopmental disorders, especially in children with heritable deficits in calcium signaling associated with autism. ![]() RyR activity contributes to dynamic remodeling of dendritic architecture in response to NDL PCBs via CaMKI-CREB-Wnt2 signaling in rats. Antagonism of γ-aminobutyric acid (GABA) receptors with bicuculline (BIC) phenocopied the dendrite-promoting effects of PCB-95, and pharmacological antagonism or siRNA knockdown of RyR blocked BIC-induced dendritic growth in dissociated and slice cultures of hippocampal neurons. Blocking CaMKK, CaMKIα/γ, MEK/ERK, CREB, or Wnt2 prevented PCB-95-induced dendritic growth. As determined by Western blotting and quantitative polymerase chain reaction, PCB-95 also activated CREB and up-regulated Wnt2. We tested the hypothesis that the CaMKI-CREB-Wnt2 signaling pathway couples NDL PCB-enhanced RyR activity to dendritic arborization.Ĭa(2+) imaging of dissociated cultures of primary rat hippocampal neurons indicated that PCB-95 (2,2',3,5'6-pentachlorobiphenyl a potent RyR potentiator), enhanced synchronized Ca(2+) oscillations in somata and dendrites that were blocked by ryanodine. RyRs regulate the spatiotemporal dynamics of intracellular Ca(2+) signals, but whether RyRs promote dendritic growth via modulation of this signaling pathway is not known. Activity-dependent dendritic growth, which is a critical determinant of neuronal connectivity in the developing brain, is mediated by calcium ion (Ca(2+))-dependent activation of Ca(2+)/calmodulin kinase-I (CaMKI), which triggers cAMP response element binding protein (CREB)-dependent Wnt2 transcription. Non-dioxin-like (NDL) polychlorinated biphenyls (PCBs) promote dendritic growth in hippocampal neurons via ryanodine receptor (RyR)-dependent mechanisms however, downstream signaling events that link enhanced RyR activity to dendritic growth are unknown.
0 Comments
Leave a Reply. |
AuthorWrite something about yourself. No need to be fancy, just an overview. ArchivesCategories |