Serotonin and/or norepinephrine elicit the secretion of BDNF into the media from hippocampal neurons in a doseand time-dependent manner. Serotonin caused significantly more BDNF secretion at 10, 30, and 60 min than at 5 min (p ≤ 0.005); norepinephrine elicited significantly more BDNF secretion at 120 min than at 5, 10, 30, and 60 min (p ≤ 0.004); norepinephrine elicited significantly more BDNF secretion at 240 min than at either 120 (p < 0.0001) or 480 (p < 0.001) min; and both neurotransmitters combined elicited as much as 2-5 times the amount elicited by vehicle alone at all time points. Among the combination treatment itself, there was a statistically significant decrease in BDNF secretion at 30 min, compared to that at 5 min (p = 0.022) and a lower, but not statistically significantly lower, than that at 60 min (p = 0.077). *, statistically significantly different from that of vehicle controls at the same corresponding time point at p < 0.05. #: significantly different at p < 0.05. Data are the mean ± SEM. Each experiment was conducted at least twice, with each sample measured in triplicate.

Serotonin and/or norepinephrine elicit the secretion of BDNF into the media from hippocampal neurons in a doseand time-dependent manner. Serotonin caused significantly more BDNF secretion at 10, 30, and 60 min than at 5 min (p ≤ 0.005); norepinephrine elicited significantly more BDNF secretion at 120 min than at 5, 10, 30, and 60 min (p ≤ 0.004); norepinephrine elicited significantly more BDNF secretion at 240 min than at either 120 (p < 0.0001) or 480 (p < 0.001) min; and both neurotransmitters combined elicited as much as 2-5 times the amount elicited by vehicle alone at all time points. Among the combination treatment itself, there was a statistically significant decrease in BDNF secretion at 30 min, compared to that at 5 min (p = 0.022) and a lower, but not statistically significantly lower, than that at 60 min (p = 0.077). *, statistically significantly different from that of vehicle controls at the same corresponding time point at p < 0.05. #: significantly different at p < 0.05. Data are the mean ± SEM. Each experiment was conducted at least twice, with each sample measured in triplicate.

Citations

... It was previously shown that treating primary cultures of hippocampal neurons with norepinephrine increases BDNF levels [26]. Furthermore, serotonin and norepinephrine differentially increase BDNF expression [46]. This is in line with our results in which, norepinephrine, but not serotonin, induced an increase in both exogenous and endogenous BDNF. ...
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... It was previously shown that treating primary cultures of hippocampal neurons with norepinephrine increases BDNF levels [26]. Furthermore, serotonin and norepinephrine differentially increase BDNF expression [43]. This is in line with our results in which, ...
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Antidepressants are known for their neurotrophic effects, particularly through the regulation of brain-derived neurotrophic factor (BDNF) expression. Mirtazapine, a tetracyclic noradrenergic and specific serotonergic antidepressant (NaSSA) has been observed to upregulate BDNF, though its underlying mechanism remains unclear. In this study, we used the human neuroblastoma SH-SY5Y cell line to investigate whether mirtazapine could enhance BDNF translation by modulating serotonin and/or norepinephrine and their receptors. A 1-hour stimulation with 1 or 10 µM mirtazapine led to downregulation of serotonergic receptors 5HT1A, while increasing ADRA2A and ADRB2 receptors. Mirtazapine at 10 µM upregulated endogenous BDNF after 3h, but not 1h stimulation. To investigate the translation of major BDNF transcripts, we used chimeric BDNF-luciferase constructs with the untranslated 5'UTR exons I, IIc, IV, or VI, and the long version of the 3'UTR. Luciferase assays and Western blotting revealed that mirtazapine selectively enhanced exon-IIc-BDNF-long3'UTR-Luciferase translation. This increase was associated with norepinephrine release and was inhibited by blocking ADRA2A or ADRB2 adrenoceptors for the exon-IIc-BDNF-long3'UTR-Luciferase, and ADR2B for endogenous BDNF. These findings provide a new perspective on the critical role of the noradrenergic system in mediating mirtazapine’s effects on BDNF translation. We propose a novel mechanism of action in which mirtazapine promotes norepinephrine release and noradrenergic responses by upregulating ADRA2A and ADRB2 while downregulating serotonergic receptors.
... Norepinephrine induces phosphorylation of cAMP-response element binding protein (CREB) and stimulates expression of both BDNF and nerve growth factor (NGF) (Counts and Mufson, 2010). Also, norepinephrine activates phosphatidylinositol-3 kinase (PI-3K)/Akt and mitogenactivated protein kinase (MAPK) and NO/cGMP pathways, in hippocampal neurons (Chen and Russo-Neustadt, 2013). BDNF activates the Trk receptor and participate in neuron plasticity, growth, development and survival of neurons. ...
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... SDS-PAGE/Western blotting has been described in great detail elsewhere [49]. ...
... В процессах сенситизации терминалей тройничного нерва доказано участие фактора транскрипции CREB и регулируемого им нейротрофина BDNF [37]. Белок BDNF необходим для поддержания нейрональной передачи, опосредованно через модуляцию активности AMPA-глутаматных рецепторов обеспечивает баланс глутаматергической и ГАМКэргичности систем, влияя на проведение болевой чувствительности. ...
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