Promoting the hippocampal PPARα expression participates in the antidepressant mechanism of reboxetine, a selective norepinephrine reuptake inhibitor

Gao, Shangyan; Zhang, Xueling; Xu, Hui; Miao, Dongjin; Qian, Jiaoni; Wu, Zhiyong; Shi, Weixiang

doi:10.1016/j.bbr.2021.113535

Cited by 6 publications

(3 citation statements)

References 43 publications

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“…A limitation of this study is the lack of data on the effects of reboxetine on normoglycemic rats, as reboxetine treatment may also cause significant changes independent of diabetic conditions. Indeed, previous studies reporting a direct effect of reboxetine on brain BDNF levels in healthy (51,52) and depressed (53,54,55) subjects may point to the potential of this drug to alter spinal neurotrophin levels. Similarly, reboxetine may also have direct effects on synaptophysin levels.…”

Section: Discussionmentioning

confidence: 96%

Effect of Reboxetine Treatment on BDNF, Synaptophysin, and PSD-95 Levels in the Spinal Dorsal Horn of Rats with Diabetic Neuropathy

TURAN YÜCEL,

ÜÇEL,

DEMİR ÖZKAY

et al. 2023

Clinical and Experimental Health Sciences

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Objective: It is known that neuropathic pain is accompanied by alterations in the levels of neurotrophic factors and synaptic proteins in the microenvironment of the spinal dorsal horn. Such changes contribute to hyperalgesia and allodynia processes; thus, analgesic drugs can exert their pharmacological effects by affecting the expressions, levels, or functions of these endogenous substances. In this study, based on the knowledge that reboxetine (a selective noradrenaline reuptake inhibitor) has the potential for antihyperalgesic efficacy in diabetic neuropathy, we aimed to examine the probable effects of this drug on diabetes-induced changes in brain-derived neurotrophic factor (BDNF), synaptophysin (the pre-synaptic marker of synaptic integration), and postsynaptic density-95 (PSD-95) (the postsynaptic marker of synaptic integration) levels in the superficial laminae of the dorsal horn. Methods: Experimental diabetes was induced by a single-dose injection of streptozotocin (STZ) (50 mg/kg) in rats. After four week-long induction period of painful diabetic neuropathy, rats were treated orally with 8 mg/kg reboxetine for two weeks. Hyperalgesia responses were evaluated by using the Randall–Selitto and Hargreave's tests. Following the pain tests, immunohistochemical studies were performed. Results: Two weeks of reboxetine administration increased the reduced paw withdrawal thresholds and shortened the paw withdrawal latencies of diabetic rats in neuropathic pain tests, indicating the antihyperalgesic efficacy of this drug. Moreover, augmented BDNF and synaptophysin levels in diabetic rats reversed by reboxetine treatment. However, there was no alteration in the densities of PSD-95, in both STZ-diabetic and reboxetine-treated STZ-diabetic rats. Conclusion: The obtained results suggested that inhibition of central sensitization and modulation of spinal plasticity seem to be pharmacological mechanisms underlying reboxetine's antihyperalgesic effects on diabetic rats. However, further studies are still needed to clarify the exact mechanism of action.

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Section: Discussionmentioning

confidence: 96%

Effect of Reboxetine Treatment on BDNF, Synaptophysin, and PSD-95 Levels in the Spinal Dorsal Horn of Rats with Diabetic Neuropathy

TURAN YÜCEL,

ÜÇEL,

DEMİR ÖZKAY

et al. 2023

Clinical and Experimental Health Sciences

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“…This method was done as we described before ( Wu et al, 2018 ; Chen et al, 2019 ; Gao et al, 2022 ). Protein samples of 30 μg were loaded on 10/12% SDS-PAGE gels (Beyotime, Shanghai, China).…”

Section: Methodsmentioning

confidence: 99%

Antidepressant-like activity of oroxylin A in mice models of depression: A behavioral and neurobiological characterization

Fan

Gao

et al. 2022

Front. Pharmacol.

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Depression is a mood disorder which causes a huge economic burden to both families and societies. However, those monoamine-based antidepressants used in clinical practice have been found to have various limitations. Therefore, currently it is very necessary to explore novel antidepressant targets and medications. As a main active component extracted from Scutellariae radix, oroxylin A possesses many pharmacological functions such as anti-cancer, anti-inflammation and neuroprotection. Here, the present study aims to investigate whether oroxylin A possess antidepressant-like actions using the chronic unpredictable mild stress (CUMS) and chronic restraint stress (CRS) models of depression, forced swim test, tail suspension test, open field test, sucrose preference test, western blotting, immunofluorescence and viral-mediated gene interference. Our results revealed that treatment of oroxylin A fully prevented both the CUMS-induced and CRS-induced depressive-like behaviors in mice. Moreover, the protecting effects of oroxylin A against CUMS and CRS on mice behaviors were accompanied with a significant enhancement on the levels of brain-derived neurotrophic factor (BDNF), phosphorylated tyrosine kinase B (pTrkB), phosphorylated cAMP-response element binding protein (pCREB) and neurogenesis in the hippocampus. Furthermore, genetic knockdown of BDNF and TrkB in the hippocampus remarkably abolished the antidepressant-like efficacy of oroxylin A in both the CUMS and CRS models of depression, proving that the hippocampal BDNF-TrkB system participates in the antidepressant mechanism of oroxylin A. In summary, our findings are the first evidence showing that oroxylin A possesses potential of being an antidepressant candidate.

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“…Reboksetin'in diyabetik hayvanların artmış olan anksiyete düzeylerini azalttığını ortaya koyan bu bulgular, doğrudan bu ilacın anksiyolitik etkinliği [57][58][59] ile ilişkili olabilir. Diğer yandan reboksetinin SSS'de nörotrofik faktörleri destekleyici [60,61] ve nöroinflamasyonu/ nörodejenerasyonu azaltıcı [62] etkilerinin de, bu ilacın diyabet ile indüklenen emosyonel bozukluklara karşı etkinliğine katkıda bulunmuş olması mümkündür. Bonferroni testi sonuçları, tedavi edilmeyen diyabetik hayvanların dört gün boyunca kaydedilen platformu bulma sürelerinin, normoglisemik kontrol hayvanlarına göre uzun olduğuna işaret etmiştir.…”

Section: Yükseltilmiş Artı şEkilli Labirent Testine İlişkin Bulgularunclassified

Rebokseti̇n’i̇n Di̇yabeti̇k Siçanlarda Bozulmuş Davraniş Parametreleri̇ Üzeri̇ndeki̇ Yararli Etki̇leri̇

Yücel

Kandemir

Üçel

et al. 2022

Ankara Ecz. Fak. Derg.

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Amaç: Diyabetik hastalarda duygu-durum hastalıklarının ve kognitif bozukluk insidansının genel popülasyona oranla daha yüksek olduğu bilinmektedir. Bu çalışmada, klinikte antidepresan etkinliği için reçete edilen reboksetin’in sıçanlarda diyabet ile indüklenen davranışsal ve bilişsel değişiklikler üzerine etkinliğinin araştırılması amaçlanmıştır. Gereç ve Yöntem: Sıçanlarda deneysel diyabet modeli 50 mg/kg tek doz streptozotosin enjeksiyonu (i.v.) ile oluşturulnuştur. Reboksetin tedavisine diyabetik komplikasyonların oluşması için 4 hafta beklendikten sonra başlanmıştır. Deney hayvanlarının depresyon ve anksiyete düzeyleri sırasıyla modifiye zorlu yüzme ve yükseltilmiş artı şekilli labirent testleri ile araştırılmış; kognitif performansları ise Morris su tankı ve pasif sakınma testleri ie değerlendirilmiştir. Hayvanlarının motor aktiviteleri de aktivite kafesi ve Rota-rod testleri ile incelenmiştir. Sonuç ve Tartışma: Deneyler sonucunda, diyabetik sıçanların depresyon ve anksiyete düzeylerinin yükseldiği ve bilişsel performanslarının zayıfladığı belirlenmiştir. İki hafta süre ile uygulanan reboksetin tedavisi (8 ve 16 mg/kg) diyabetik sıçanların yüksek depresyon ve anksiyete düzeylerini azaltırken, zayıflamış olan bilişsel performanslarını kayda değer ölçüde güçlendirmiştir. Elde edilen bulgular reboksetin’in diyabete bağlı olarak ortaya çıkan davranışsal ve bilişsel bozuklukların tedavisinde terapötik bir potansiyele sahip olabileceğine işaret etmiştir.

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Promoting the hippocampal PPARα expression participates in the antidepressant mechanism of reboxetine, a selective norepinephrine reuptake inhibitor

Cited by 6 publications

References 43 publications

Effect of Reboxetine Treatment on BDNF, Synaptophysin, and PSD-95 Levels in the Spinal Dorsal Horn of Rats with Diabetic Neuropathy

Effect of Reboxetine Treatment on BDNF, Synaptophysin, and PSD-95 Levels in the Spinal Dorsal Horn of Rats with Diabetic Neuropathy

Antidepressant-like activity of oroxylin A in mice models of depression: A behavioral and neurobiological characterization

Rebokseti̇n’i̇n Di̇yabeti̇k Siçanlarda Bozulmuş Davraniş Parametreleri̇ Üzeri̇ndeki̇ Yararli Etki̇leri̇

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