Lack of bombesin receptor-activated protein homologous protein impairs hippocampal synaptic plasticity and promotes chronic unpredictable mild stress induced behavioral changes in mice

Yao, Xueping; Qin, Xiaoqun; Wang, Hui; Zheng, Jiaoyun; Peng, Zhi Fei; Wang, Jie; Weber, H. Christian; Liu, Rujiao; Zhang, Wenrui; Zeng, Ji; Zuo, Suhui; Chen, Hui; Xiang, Yang; Liu, Chi; Liu, Huijun; Pan, Lang; Qu, Xiangping

doi:10.1080/10253890.2022.2155513

Cited by 5 publications

(7 citation statements)

References 40 publications

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“…However, in this study, we did not further analyze the functional relationship between BRAP and BRS-3 according to the following considerations. First, the interaction between BRAP and BRS-3 was not further verified, either by the yeast two-hybrid experiment using the plasmid expressing full length BRAP, or by co-immunoprecipitation using protein extract of 16HBE14o-, an immortalized human bronchial epithelial cell line that expresses both BRAP and BRS-3 13 . Second, there is no evidence to show the activation effect of BRAP on BRS-3.…”

Section: Discussionmentioning

confidence: 99%

“…However, when those mice were induced to develop some diseases, they exhibited alterations in disease phenotypes compared with their wild type controls. Those diseases developed in mice include asthma-like inflammation in lungs induced by oval albumin (OVA) or house dust mites (HDM) (data not published), lung injury and fibrosis induced by bleomycin 12 , behavioral changes induced by chronic unpredictable mild stress (CUMS) 13 , renal injury and fibrosis induced either by unilateral ureteral obstruction (UUO) or combined treatment of high fat diet (HFD) and streptozocin (STZ) (data not published). By using those animal disease models we found that BRAP deficiency caused various functional changes in different cell types, which might contribute to alterations in disease phenotypes.…”

Section: Discussionmentioning

confidence: 99%

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Bombesin receptor-activated protein homolog deficiency altered the pattern of pathological changes of psoriasis - like skin lesion in mice

Zheng,

Wang,

Wang

et al. 2024

Int. J. Med. Sci.

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This study investigated the potential role of the mouse homolog of bombesin receptor-activated protein (BRAP) in imiquimod (IMQ) induced psoriasis - like skin inflammation. The expression of both human BRAP, encoded by C6orf89 , and its mouse homolog, encoded by BC004004 , has been found to be expressed abundantly in the keratinocytes. BC004004 knockout mice ( BC004004 -/- ) were topically treated with IMQ daily for 7 days to test whether they were more vulnerable to psoriasis - like inflammation. We found that those mice exhibited an altered pattern of inflammation process compared to isogenic wild type control mice ( BC004004 +/+ ). BC004004 -/- mice developed skin lesions with earlier and more acute onset, as well as a quicker remission. The cytokines related to pathogenesis of psoriasis also exhibited different expression patterns in IMQ treated BC004004 -/- mice. On day 4 of IMQ treatment, BC004004 -/- mice exhibited a higher expression level of IL-17A compared to BC004004 +/+ mice, suggesting a more robust activation of Th17 cells in the knockout mice. The serum level of thymic stromal lymphopoietin (TSLP), one of the keratinocyte derived cytokines, was also increased in BC004004 -/- mice and reached its peak on day 4. Knockdown of BRAP in cultured human keratinocyte-derived HaCaT cells by siRNA silencing led to increased release of TSLP. Our data suggest that the elevated of level of TSLP released from keratinocytes due to BRAP deficiency might mediate the crosstalk between the epidermal cells and immune cells and thereby contributing to the altered pathological changes observed in psoriasis - like skin lesion in knockout mice.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Bombesin receptor-activated protein homolog deficiency altered the pattern of pathological changes of psoriasis - like skin lesion in mice

Zheng,

Wang,

Wang

et al. 2024

Int. J. Med. Sci.

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“…One of its functions is to participate in dendritic transport in hippocampal neurons [39]. We have found that BC004004 −/− mice exhibited decreased dendritic length and increased amounts of immature spines, as well as altered expression pattern of synaptic‐related proteins including GluN2A, synaptophysin, and BDNF in the hippocampus region [48]. It is likely that the interaction between BRAP and Rabin8 may affect the levels of GTP‐bound form of Rab8 and thus contribute to the regulation of dendritic function.…”

Section: Discussionmentioning

confidence: 99%

Knockout of the BRAP homolog in mice leads to abnormal tracheal cilia

Wang,

Zuo,

Zheng

et al. 2023

FEBS Letters

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Both bombesin receptor‐activated protein (BRAP) and its mouse homolog have been found to be expressed in bronchial epithelia but with unclear functions. Using electron microscopy combined with histological assays, we found that BRAP homolog deficiency in mice led to abnormal tracheal cilia. Rab‐3A‐interacting protein (Rabin8), a protein that might play a role in cilia development, was screened by yeast two‐hybrid and further verified to have interaction with human BRAP by co‐immunoprecipitation and pull down assays. The expression levels of Rabin 8, together with acetylated α‐tubulin, a marker of cilia, were either downregulated by knockdown of BRAP or upregulated by overexpression of BRAP in cultured immortalized human bronchial epithelial cells. These results reveal a role for BRAP in airway cilia formation.

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“…The gene C6orf89 encodes the bombesin receptor-activated protein (BRAP) which might be involved in the stress response of lung epithelia (Liu et al, 2016;Xu et al, 2017) and can be linked to allergic rhinitis and asthma. In mice, the BRAP homologous protein may have a protective effect on the behavioral response to stress via regulating dendritic spine formation and synaptic plasticity in the hippocampus (Yao et al, 2023). As a consequence, it was concluded that chronic stress might cause damage to hippocampus function (Yao et al, 2023) A link towards the role of PNLDC1 instead could not be found.…”

Section: Discussionmentioning

confidence: 99%

“…In mice, the BRAP homologous protein may have a protective effect on the behavioral response to stress via regulating dendritic spine formation and synaptic plasticity in the hippocampus (Yao et al, 2023). As a consequence, it was concluded that chronic stress might cause damage to hippocampus function (Yao et al, 2023) A link towards the role of PNLDC1 instead could not be found.…”

Section: Discussionmentioning

confidence: 99%

Impact of gene-by-trauma interaction in MDD-related multimorbidity clusters

Bonk,

Eszlari,

Kirchner

et al. 2023

Preprint

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Background: Major depressive disorder (MDD) is considerably heterogeneous in terms of comorbidities, which may hamper the disentanglement of its biological mechanism. In a previous study, we classified the lifetime trajectories of MDD-related multimorbidities into seven distinct clusters, each characterized by unique genetic and environmental risk-factor profiles. The current objective was to investigate genome-wide gene-by-environment (G×E) interactions with childhood trauma burden, within the context of these clusters. Methods: We analyzed 76,856 participants and 3,875,386 single-nucleotide polymorphisms (SNPs) of the UK Biobank database. Childhood trauma burden was assessed using the Childhood Trauma Screener (CTS). For each cluster, Plink 2.0 was used to calculate SNP×CTS interaction effects on the participants’ cluster membership probabilities. We especially focused on the effects of 31 candidate genes and associated SNPs selected from previous G×E studies for childhood maltreatment’s association with depression. Results: At SNP-level, only the high-multimorbidity Cluster 6 revealed a genome-wide significant SNP rs145772219. At gene-level, LDLRAD4 was genome-wide significant for the low-multimorbidity Cluster 1 and C6orf89and TAAR2 for the high-multimorbidity Cluster 7. Regarding candidate SNPs for G×E interactions, individual SNP results could be replicated for specific clusters. The candidate genes DRD2 (Cluster 1), and DBH and MTHFR (both Cluster 5), and TPH1(Cluster 6) survived multiple testing correction. Limitations: CTS is a short retrospective self-reported measurement. Clusters could be influenced by genetics of individual disorders. Conclusions: The first G×E GWAS for MDD-related multimorbidity trajectories successfully replicated findings from previous G×E studies related to depression, and revealed risk clusters for the contribution of childhood trauma.

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Lack of bombesin receptor-activated protein homologous protein impairs hippocampal synaptic plasticity and promotes chronic unpredictable mild stress induced behavioral changes in mice

Cited by 5 publications

References 40 publications

Bombesin receptor-activated protein homolog deficiency altered the pattern of pathological changes of psoriasis - like skin lesion in mice

Bombesin receptor-activated protein homolog deficiency altered the pattern of pathological changes of psoriasis - like skin lesion in mice

Knockout of the BRAP homolog in mice leads to abnormal tracheal cilia

Impact of gene-by-trauma interaction in MDD-related multimorbidity clusters

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