CRTC1 signaling involvement in depression-like behavior of prenatally stressed offspring rat

Si, Yufang; Xue, Xing; Liu, Si; Chen, Feng; Zhang, Huiping; Zhang, Sisi; Ren, Yating; Ma, Hengyu; Dong, Yankai; Li, Hui; Xie, Longshan; Zhu, Zhongliang

doi:10.1016/j.bbr.2020.113000

Cited by 12 publications

(5 citation statements)

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“…In our experiment, the Tukey’s test did not reveal any difference in the mRNA levels of Creb , Bdnf , Ntrk2a, and Ngfra genes in zebrafish treated with fluoxetine and fluoxetine together with pCPA compared with the control ones. These results agree with data obtained earlier on rodents [ 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 ] and zebrafish [ 48 ] and indicate that the BDNF system in zebrafish is resistant to prolonged fluoxetine treatment.…”

Section: Discussionsupporting

confidence: 92%

Tryptophan Hydroxylase 2 Deficiency Modifies the Effects of Fluoxetine and Pargyline on the Behavior, 5-HT- and BDNF-Systems in the Brain of Zebrafish (Danio rerio)

Evsiukova

Базовкина

Bazhenova

et al. 2021

IJMS

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The mechanisms of resistance to antidepressant drugs is a key and still unresolved problem of psychopharmacology. Serotonin (5-HT) and brain-derived neurotrophic factor (BDNF) play a key role in the therapeutic effect of many antidepressants. Tryptophan hydroxylase 2 (TPH2) is the rate-limiting enzyme in 5-HT synthesis in the brain. We used zebrafish (Danio rerio) as a promising model organism in order to elucidate the effect of TPH2 deficiency caused by p-chlorophenylalanine (pCPA) on the alterations in behavior and expression of 5-HT-related (Tph2, Slc6a4b, Mao, Htr1aa, Htr2aa) and BDNF-related (Creb, Bdnf, Ntrk2a, Ngfra) genes in the brain after prolonged treatment with two antidepressants, inhibitors of 5-HT reuptake (fluoxetine) and oxidation (pargyline). In one experiment, zebrafish were treated for 72 h with 0.2 mg/L fluoxetine, 2 mg/L pCPA, or the drugs combination. In another experiment, zebrafish were treated for 72 h with 0.5 mg/L pargyline, 2 mg/L pCPA, or the drugs combination. Behavior was studied in the novel tank diving test, mRNA levels were assayed by qPCR, 5-HT and its metabolite concentrations were measured by HPLC. The effects of interaction between pCPA and the drugs on zebrafish behavior were observed: pCPA attenuated “surface dwelling” induced by the drugs. Fluoxetine decreased mRNA levels of Tph2 and Htr2aa genes, while pargyline decreased mRNA levels of Slc6a4b and Htr1aa genes. Pargyline reduced Creb, Bdnf and Ntrk2a genes mRNA concentration only in the zebrafish treated with pCPA. The results show that the disruption of the TPH2 function can cause a refractory to antidepressant treatment.

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Section: Discussionsupporting

confidence: 92%

Tryptophan Hydroxylase 2 Deficiency Modifies the Effects of Fluoxetine and Pargyline on the Behavior, 5-HT- and BDNF-Systems in the Brain of Zebrafish (Danio rerio)

Evsiukova

Базовкина

Bazhenova

et al. 2021

IJMS

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“…Recently, several studies highlighted the importance of CRTC1 in stress-and inflammation-induced depressive-like behaviors, thus extending our pioneering findings on the role of CRTC1 in MDD (Davis, 2019;Jiang B. et al, 2019;Ni et al, 2019;Liu et al, 2020;Wang et al, 2020;Si et al, 2021). In a quite extensive study, the SIK2-CRTC1-CREB-BDNF pathway was proved highly instrumental in mediating chronic stressinduced depressive-like behaviors and antidepressant response in C57BL/6J mice (Jiang B. et al, 2019).…”

Section: Si Et Al 2021mentioning

confidence: 83%

“…Two follow-up studies from the same laboratory then showed that the antidepressant effects of imipramine depend on CRTC1 in the medial prefrontal cortex ( Wang et al, 2020 ), and that ARN-3236, a selective inhibitor of SIK2, induced significant antidepressant-like effects in both the CSDS and CUMS models of depression by acting on the hippocampal CRTC1-CREB-BDNF pathway ( Liu et al, 2020 ). Moreover, it was recently shown that prenatally stressed offspring male rats display depressive-like behaviors associated with decreased levels of CRTC1 and BDNF in the hippocampus and prefrontal cortex, which are restored by a chronic fluoxetine treatment ( Si et al, 2021 ). Taken together, these findings strengthen the pivotal role of hippocampal and prefrontal CRTC1 in the pathogenesis of MDD and in antidepressant response.…”

Section: Emerging Role Of Creb-regulated Transcription Coactivator 1 ...mentioning

confidence: 99%

New Insights Into the Pivotal Role of CREB-Regulated Transcription Coactivator 1 in Depression and Comorbid Obesity

Rossetti

Cherix

Guiraud

et al. 2022

Front. Mol. Neurosci.

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Depression and obesity are major public health concerns, and there is mounting evidence that they share etiopathophysiological mechanisms. The neurobiological pathways involved in both mood and energy balance regulation are complex, multifactorial and still incompletely understood. As a coactivator of the pleiotropic transcription factor cAMP response element-binding protein (CREB), CREB-regulated transcription coactivator 1 (CRTC1) has recently emerged as a novel regulator of neuronal plasticity and brain functions, while CRTC1 dysfunction has been associated with neurodegenerative and psychiatric diseases. This review focuses on recent evidence emphasizing the critical role of CRTC1 in the neurobiology of depression and comorbid obesity. We discuss the role of CRTC1 downregulation in mediating chronic stress-induced depressive-like behaviors, and antidepressant response in the light of the previously characterized Crtc1 knockout mouse model of depression. The putative role of CRTC1 in the alteration of brain energy homeostasis observed in depression is also discussed. Finally, we highlight rodent and human studies supporting the critical involvement of CRTC1 in depression-associated obesity.

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“…These unexpected results contradict the previously established correlation between a hyperactive orexin system and enhanced anxiety. The established rat models of depression, including the prenatal stress (PS) model (Si et al, 2021), and the chronic unpredictable mild stress (CUMS) model (L. Li et al, 2013; Zhou et al, 2020), both exhibit reduced sucrose consumption and lower locomotor activity in the OF test, thus mimicking some symptoms of depression. Clinical and preclinical evidence indicates that reduced levels of orexin‐A in the central nervous system (CNS) are associated with the pathogenesis of depression (Brundin et al, 2007; Stanquini et al, 2020), and that orexin‐A administration triggers an antidepressant‐like effect (Stanquini et al, 2020).…”

Section: Discussionmentioning

confidence: 99%

The effects of orexin‐A and orexin receptors on anxiety‐ and depression‐related behaviors in a male rat model of post‐traumatic stress disorder

Han

Shi

Han

2021

J of Comparative Neurology

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Orexin neurons play an important role in stress-related mental disorders including post-traumatic stress disorder (PTSD). Anxiety-and depression-related symptoms commonly occur in combination with PTSD. However, the role of the orexin system in mediating alterations in these affective symptoms remains unclear. The medial prefrontal cortex (mPFC) is implicated in both cognitive and emotional processing. In the present study, we investigated anxiety-and depression-related behavioral changes using the elevated plus maze, the sucrose preference test, and the open field test in male rats with single prolonged stress (SPS) induced-PTSD. The expression of orexin-A in the hypothalamus and orexin receptors (OX1R and OX2R) in the mPFC was detected and quantified by immunohistochemistry, western blotting, and realtime polymerase chain reaction. We found that the SPS rats exhibited enhanced levels of anxiety, reduced exploratory activities, and anhedonia. Furthermore, SPS resulted in reductions in the expression of orexin-A in the hypothalamus and the increased the expression of OX1R in the mPFC. The intracerebroventricular administration of orexin-A alleviated behavioral changes in SPS rats and partly restored the increased levels of OX1R in the mPFC. These results suggest that the orexin system plays a role in the anxiety-and depression-related symptoms observed in PTSD.

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CRTC1 signaling involvement in depression-like behavior of prenatally stressed offspring rat

Cited by 12 publications

References 50 publications

Tryptophan Hydroxylase 2 Deficiency Modifies the Effects of Fluoxetine and Pargyline on the Behavior, 5-HT- and BDNF-Systems in the Brain of Zebrafish (Danio rerio)

Tryptophan Hydroxylase 2 Deficiency Modifies the Effects of Fluoxetine and Pargyline on the Behavior, 5-HT- and BDNF-Systems in the Brain of Zebrafish (Danio rerio)

New Insights Into the Pivotal Role of CREB-Regulated Transcription Coactivator 1 in Depression and Comorbid Obesity

The effects of orexin‐A and orexin receptors on anxiety‐ and depression‐related behaviors in a male rat model of post‐traumatic stress disorder

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