Actions of Brain-Derived Neurotrophic Factor and Glucocorticoid Stress in Neurogenesis

Numakawa, Tadahiro; Odaka, Haruki; Adachi, Naoki

doi:10.3390/ijms18112312

Cited by 131 publications

(97 citation statements)

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“…In stressrelated disorders depletion of serotonin reduces brain BDNF levels (Chen et al, 2007;Yoshida et al, 2012;Zhou et al, 2008). On the contrary, hypo-serotonergic mouse (Tph2-/-or Pet1-/-) showed increased BDNF levels in hippocampus and prefrontal cortex (Diaz et al, 2013;Klempin et al, 2013;Kronenberg et al, 2016;Sachs et al, 2013) and humans with serotonin transporter deficiency (hyperserotonin) reduced the availability of BDNF (Molteni et al, 2010), which enhances NSCs proliferation and neurogenesis (Arsenijevic and Weiss, 1998;Numakawa et al, 2017). Our findings support the negative role of serotonin on BDNF signaling and NSC plasticity.…”

Section: Discussionsupporting

confidence: 73%

Neuron-glia interaction through Serotonin-BDNF-NGFR axis enables regenerative neurogenesis in Alzheimer’s model of adult zebrafish brain

Bhattarai

Coşacak

Mashkaryan

et al. 2019

Preprint

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It was recently suggested that supplying the brain with new neurons could counteract Alzheimer's disease. This provocative idea requires further testing in experimental models where the molecular basis of disease-induced neuronal regeneration could be investigated. We previously found that zebrafish stimulates neural stem cell (NSC) plasticity and neurogenesis in Alzheimer's disease and could help to understand the mechanisms to be harnessed for develop new neurons in diseased mammalian brains. Here, by performing singlecell transcriptomics, we found that Amyloid toxicity-induced Interleukin-4 induces NSC proliferation and neurogenesis by suppressing the tryptophan metabolism and reducing the production of Serotonin. NSC proliferation was suppressed by Serotonin via downregulation of BDNF-expression in Serotoninresponsive periventricular neurons. BDNF enhances NSC plasticity and neurogenesis via NGFRA/NFkB signaling in zebrafish but not in rodents. Collectively, our results suggest a complex neuron-glia interaction that regulates regenerative neurogenesis after Alzheimer's disease conditions in zebrafish. Key findings-Amyloid-induced Interleukin-4 suppresses Serotonin (5-HT) production in adult zebrafish brain -5-HT affects htr1-expresing neurons and suppresses bdnf expression -BDNF enhances plasticity in neural stem cells via NGFRA/NFkB signaling -BDNF/NGFRA signaling is a neuro-regenerative mechanism in zebrafish but not in mammals.

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Section: Discussionsupporting

confidence: 73%

Neuron-glia interaction through Serotonin-BDNF-NGFR axis enables regenerative neurogenesis in Alzheimer’s model of adult zebrafish brain

Bhattarai

Coşacak

Mashkaryan

et al. 2019

Preprint

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“…In stress-related disorders, depletion of serotonin reduces brain BDNF levels [63][64][65]. On the contrary, hyposerotonergic mouse (Tph2−/− or Pet1−/−) showed increased BDNF levels in the hippocampus and prefrontal cortex [60][61][62]66], and humans with SERT deficiency (hyperserotonin) reduced the availability of BDNF [67], which enhances NSCs proliferation and neurogenesis [68,69]. Our findings support the negative role of serotonin on BDNF signaling and NSC plasticity.…”

Section: Discussionsupporting

confidence: 72%

Neuron-glia interaction through Serotonin-BDNF-NGFR axis enables regenerative neurogenesis in Alzheimer’s model of adult zebrafish brain

et al. 2020

View full text Add to dashboard Cite

It was recently suggested that supplying the brain with new neurons could counteract Alzheimer's disease (AD). This provocative idea requires further testing in experimental models in which the molecular basis of disease-induced neuronal regeneration could be investigated. We previously found that zebrafish stimulates neural stem cell (NSC) plasticity and neurogenesis in AD and could help to understand the mechanisms to be harnessed for developing new neurons in diseased mammalian brains. Here, by performing single-cell transcriptomics, we found that amyloid toxicity-induced interleukin-4 (IL4) promotes NSC proliferation and neurogenesis by suppressing the tryptophan metabolism and reducing the production of serotonin. NSC proliferation was suppressed by serotonin via down-regulation of brain-derived neurotrophic factor (BDNF)-expression in serotonin-responsive periventricular neurons. BDNF enhances NSC plasticity and neurogenesis via nerve growth factor receptor A (NGFRA)/ nuclear factor 'kappa-light-chain-enhancer' of activated B-cells (NFkB) signaling in zebrafish but not in rodents. Collectively, our results suggest a complex neuron-glia interaction that regulates regenerative neurogenesis after AD conditions in zebrafish. OPEN ACCESS Citation: Bhattarai P, Cosacak MI, Mashkaryan V, Demir S, Popova SD, Govindarajan N, et al. (2020) Neuron-glia interaction through Serotonin-BDNF-NGFR axis enables regenerative neurogenesis in Alzheimer's model of adult zebrafish brain. PLoS Biol 18(1): e3000585. https://doi.

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“…Another potential antidepressant mechanism of puerarin (1) and estrogen involves the upregulation of BDNF mRNA expression in the hippocampus. The neurotrophin BDNF has been shown to play an important role not only in the hippocampal synaptic plasticity, the neurobiological basis of learning and memory, but also in emotional performance, such as depression, both of which are mediated by synaptogenesis [36], neurogenesis [37,38], changes in morphologies of cells and dendrites [39], and a modulation of the efficacy of neurotransmitter release [40]. Previous studies showed that patients with depression, as well as various animal models of depression, had reduced BDNF levels in the hippocampus.…”

Section: Discussionmentioning

confidence: 99%

Effects of Puerarin on the Ovariectomy-Induced Depressive-Like Behavior in ICR Mice and Its Possible Mechanism of Action

et al. 2019

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Daily treatment of ovariectomized (OVX) ICR mice with puerarin, a glycosyl isoflavone isolated from the root bark of Pueraria candollei var. mirifica, and 17β-estradiol attenuated ovariectomy-induced depression-like behavior, as indicated by a decrease in immobility times in the tail suspension test (TST) and the forced swimming test (FST), an increase in the uterine weight and volume, a decrease in serum corticosterone levels, and dose-dependently normalized the downregulated transcription of the brain-derived neurotrophic factor (BDNF) and estrogen receptor (Erβ and Erα) mRNAs. Like 17β-estradiol, puerarin also inhibited ovariectomy-induced suppression of neurogenesis in the dentate gyrus of the hippocampus (increased the number of doublecortin (DCX)-immunosuppressive cells). These results suggest that puerarin exerts antidepressant-like effects in OVX animals, possibly by attenuating the OVX-induced hyperactivation of the HPA axis and/or normalizing the downregulated transcription of BDNF and ER mRNA in the brain.Molecules 2019, 24, 4569 2 of 15 depression. These symptoms can be reversed by supplementation with estrogen. A body of evidence suggests that such estrogen replacement therapy (ERT) can exert anxiolytic and antidepressant effects in menopausal females by modulating the hypothalamic-pituitary-adrenal (HPA) axis functions [3,4]. However, the drawback of ERT is its adverse effects, such as an increased risk of breast and endometrial cancers, as well as thromboembolic events [5,6]. Consequently, the long-term usage of ERT to ameliorate emotional and cognitive deficits has an obvious limitation in women. Thus, the search for new phytoestrogens, with a weak effect on reproductive organs, from natural sources continues to be an important field of research.Pueraria candollei var. mirifica is a medicinal plant used in Thai traditional medicine for its rejuvenating and estrogenic effects [7]. For this reason, this plant has been widely investigated for its constituents and pharmacological activities. Peerakam et al. [8] found that the 95% ethanol extract of this plant contained puerarin (1), as a major compound, and other isoflavonoids, such as daidzin, daidzein, genistin, and genistein, in addition to the phytoestrogens miroestrol and deoxymiroestrol. Suthon et al.[9] evaluated the anti-osteoporotic effects of the crude extract of P. candollei var. mirifica and puerarin (1) in ovariectomized (OVX) mice and found that only the crude extract at 50 mg/kg (body weight) per day caused a significant increase in the trabecular bone mineral densities of tibia metaphysis when compared to the control group. On the other hand, the pharmacological activities of puerarin (1) (Figure 1), a major isoflavonoid from P. candollei var. mirifica, have been extensively investigated. Puerarin (1) has been widely used in the treatment of diabetes, dyslipidemia, liver fibrosis, cardiovascular diseases, neurotoxicity, and Alzheimer's disease [10]. This compound was also found to exhibit various protective effects against fever, hyper...

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Actions of Brain-Derived Neurotrophic Factor and Glucocorticoid Stress in Neurogenesis

Cited by 131 publications

References 96 publications

Neuron-glia interaction through Serotonin-BDNF-NGFR axis enables regenerative neurogenesis in Alzheimer’s model of adult zebrafish brain

Neuron-glia interaction through Serotonin-BDNF-NGFR axis enables regenerative neurogenesis in Alzheimer’s model of adult zebrafish brain

Neuron-glia interaction through Serotonin-BDNF-NGFR axis enables regenerative neurogenesis in Alzheimer’s model of adult zebrafish brain

Effects of Puerarin on the Ovariectomy-Induced Depressive-Like Behavior in ICR Mice and Its Possible Mechanism of Action

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