PKA-CREB-BDNF signaling regulated long lasting antidepressant activities of Yueju but not ketamine

Xue, Wenhao; Wang, Wei; Gong, Tong; Zhang, Hailou; Tao, Weiwei; Xue, Lihong; Sun, Yan; Wang, Fushun; Chen, Gang

doi:10.1038/srep26331

Cited by 91 publications

(67 citation statements)

References 39 publications

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“…Our results showed that thioperamide upregulated the BDNF levels, and inhibition of CREB by H89 compromised this effect, suggesting thioperamide promote neural stem cell proliferation through enhancing transcription of BDNF via activating CREB. Our results were consistent with study that activation of PKA/CREB signaling showed ameliorated depressive behaviors through upregulating BDNF expression (Xue et al, 2016), showing that strategies activating CREB/BDNF pathway are beneficial to neurogenesis. Neurotrophins, especially BDNF, are potent modulators of dendritic development.…”

Section: Discussionsupporting

confidence: 92%

Histamine H3 Receptor Antagonist Enhances Neurogenesis and Improves Chronic Cerebral Hypoperfusion-Induced Cognitive Impairments

Wang

Liu

et al. 2020

Front. Pharmacol.

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Chronic cerebral hypoperfusion (CCH) is a neurodegenerative disease, which induces cognitive impairments in the central nervous system (CNS). Histamine H3 receptor (H3R) is an autoreceptor involved in the modulation of neurogenesis and synaptic plasticity in the CNS. However, the role of H3R in CCH-induced injury and the related mechanisms remain to be clarified. Here, we found that thioperamide (THIO), a H3R antagonist, promotes the proliferation of NE-4C stem cells under either normal or oxygen-glucose deprivation (OGD) condition in vitro. Thioperamide promotes the phosphorylation of cAMP-response element binding (CREB), and thereby upregulates the expression and release of brain-derived neurotrophic factor (BDNF). However, H89, an inhibitor of protein kinase A (PKA)/CREB, reverses the effects of thioperamide on either BDNF expression and release or cell proliferation in NE-4C stem cells. Moreover, thioperamide has protective effects on OGDinduced impairment of cell viability and neuronal morphology in primary neurons in vitro. Furthermore, thioperamide enhanced neurogenesis in the dentate gyrus (DG) and subventricular zone (SVZ) regions in vivo, and ameliorated CCH-induced cognitive impairments. Taken together, these findings showed that thioperamide protects primary neurons against OGD-induced injury and promotes the proliferation of neural stem cells in DG and SVZ regions through CREB/BDNF pathways, thereby improving cognitive deficit.

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Section: Discussionsupporting

confidence: 92%

Histamine H3 Receptor Antagonist Enhances Neurogenesis and Improves Chronic Cerebral Hypoperfusion-Induced Cognitive Impairments

Wang

Liu

et al. 2020

Front. Pharmacol.

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“…CREB is an important regulator for BDNF and GDNF expression [43–45]. Chronic antidepressant treatment enhances CREB activation, suggesting CREB as an important mediator for antidepressant treatment [24].…”

Section: Resultsmentioning

confidence: 99%

N-3 polyunsaturated fatty acids promote astrocyte differentiation and neurotrophin production independent of cAMP in patient-derived neural stem cells

Wang

Sheridan

et al. 2020

Preprint

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30Evidence from epidemiological and laboratory studies, as well as randomized placebo-controlled 31 trials, suggests supplementation with n-3 polyunsaturated fatty acids (PUFAs) may be efficacious 32 for treatment of major depressive disorder (MDD). The mechanisms underlying n-3 PUFAs 33 potential therapeutic properties remain unknown. There are suggestions in the literature that glial 34 hypofunction is associated with depressive symptoms and that antidepressants may normalize 35 glial function. In this study, iPSC-derived neuronal stem cell lines were generated from 36 individuals with MDD. Astrocytes differentiated from patient-derived neuronal stem cells 37 (iNSCs) were verified by GFAP. Cells were treated with eicosapentaenoic acid (EPA), 38 docosahexaenoic acid (DHA) and stearic acid (SA). During astrocyte differentiation, we found 39 that n-3 PUFAs increased GFAP expression and GFAP positive cell formation. BDNF and 40 GDNF production were increased in the astrocytes derived from patients subsequent to n-3 41 PUFA treatment. Stearic Acid (SA) treatment did not have this effect. CREB activity 42 (phosphorylated CREB) was also increased by DHA and EPA but not by SA. Furthermore, when 43 these astrocytes were treated with n-3 PUFAs, the cAMP antagonist, RP-cAMPs did not block n-44 3 PUFA CREB activation. However, the CREB specific inhibitor (666-15) diminished BDNF 45 and GDNF production induced by n-3 PUFA, suggesting CREB dependence. Together, these 46 results suggested that n-3 PUFAs facilitate astrocyte differentiation, and may mimic effects of 47 some antidepressants by increasing production of neurotrophic factors. The CREB-dependence 48 and cAMP independence of this process suggests a manner in which n-3 PUFA could augment 49 antidepressant effects. These data also suggest a role for astrocytes in both MDD and 50 antidepressant action. 51 52 53Major depressive disorder (MDD) is the most common psychiatric disorder, with almost 54 one in six individuals experiencing at least one depressive episode at some point in their lifetime. 55It is currently the leading cause of disability worldwide [1, 2]. While effective treatments exist, 56 about one third of patients treated with antidepressants do not reach symptomatic remission [3, 57 4]. While some of these non-remitters may respond to ketamine or other rescue strategies, 58 additional therapeutic options are needed. 59Brain regions and even cell-types contributing to MDD are not well established [4]. 60Evidence from clinical, preclinical and post-mortem studies suggests that dysfunction and 61 degeneration of astrocytes may be one of potential candidates, and astrocytes may also represent 62 a potential therapeutic target for MDD [5][6][7][8]. Antidepressants, including SSRIs and ketamine, 63 increase brain-derived neurotrophic factor (BDNF) and glial cell-derived neurotrophic factor 64 (GDNF) expression in primary cultured animal astrocytes [9][10][11]. Substantial evidence suggested 65 that astrocytes might be the main resource of antidepressant...

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“…Simultaneously, the control groups received the same volume of vehicle. The dosage of KET was chosen according to our previous research [36]. Thereafter, the animals were subjected to TST and FST.…”

Section: Drugs and Treatmentmentioning

confidence: 99%

Anti-depressant effects of oil from fructus gardeniae via PKA-CREB-BDNF signaling

et al. 2019

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The dried ripe fruit of Gardenia jasminoides Ellis was usually applied as an herb medicine in Traditional Chinese Medicine. It was suggested that the Gardenia jasminoides oil extract (oil from Fructus Gardeniae [OFG]) might serve as a potential treatment for depression, whereas its pathogenesis still remained not fully understood. The present research was conducted to evaluate the anti-depressive effect of OFG in mice and explore its potential mechanism. The OFG and ketamine (KET) were intragastrically and intraperitoneally treated, respectively. Thereafter, the animals were subjected to the behavior tests. The expressions of protein kinase A (PKA), brain derived neurotrophic factor (BDNF), cAMP response element-binding protein (CREB) in hippocampus were detected by Western blot. The selective PKA inhibitor H-89 was also applied to confirm the mechanism. As a result, OFG and KET treatment improved the behavior performance. Furthermore, the administrations of OFG effectively enhanced the expressions of PKA, p-CREB, and BDNF. With the application of selective PKA inhibitor H-89, the ameliorated effects caused by OFG were blocked, but not by KET. In conclusion, the presented work indicated that OFG-exerted protective effect on depression through PKA-CREB-BDNF signaling.

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PKA-CREB-BDNF signaling regulated long lasting antidepressant activities of Yueju but not ketamine

Cited by 91 publications

References 39 publications

Histamine H3 Receptor Antagonist Enhances Neurogenesis and Improves Chronic Cerebral Hypoperfusion-Induced Cognitive Impairments

Histamine H3 Receptor Antagonist Enhances Neurogenesis and Improves Chronic Cerebral Hypoperfusion-Induced Cognitive Impairments

N-3 polyunsaturated fatty acids promote astrocyte differentiation and neurotrophin production independent of cAMP in patient-derived neural stem cells

Anti-depressant effects of oil from fructus gardeniae via PKA-CREB-BDNF signaling

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