FSHR ablation induces depression-like behaviors

Bi, Wen-kai; Shao, Shanshan; Li, Zhiwei; Ruan, Yongwei; Luan, Sisi; Dong, Zheng; Wang, Jing; Wu, Shanshan; Guo, Tian; Ma, Shizhan; Gao, Ling; Zhao, Jiajun; He, Zhao

doi:10.1038/s41401-020-0384-8

Cited by 14 publications

(9 citation statements)

References 44 publications

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“…It was worth noting that OG treatment significantly up‐regulated mRNA expression of FSH and FSHR in hippocampus, as well as the protein expression in OVX‐CUMS mice compared that of model group. This finding is partially consistent with the recent report that FSHR signaling activation in hippocampus resisted the depression‐like behaviors in FSHR (Fshr +/+ )‐OVX mice in OFT and TST compared to FSHR ablation (Fshr −/− )‐OVX mice, and FSHR deficiency increased cellular oxidative stress, while pretreatment FSH displayed antioxidant effect on mouse neuroblastoma N2a cells by regulating GSH metabolism (Bi, Luan, et al, 2020; Bi, Shao et al, 2020). This was unknown that how the mechanism of FSH acts on the hippocampus.…”

Section: Discussionsupporting

confidence: 91%

Orcinol glucoside improves the depressive‐like behaviors of perimenopausal depression mice through modulating activity of hypothalamic–pituitary–adrenal/ovary axis and activating BDNF‐ TrkB‐CREB signaling pathway

Zhang

et al. 2021

Phytotherapy Research

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Orcinol Glucoside (OG), a phenolic glucoside isolated from C. orchioides, showed the antidepressant-like effect on chronic unpredictable mild stress (CUMS)-induced rats previously. This study was designed to determine whether OG could improve the depressive-like symptoms of perimenopausal depression (PMD) and the possible mechanisms involved. This research was performed on a PMD mice model established by a two-steps method of ovariectomy (OVX) followed CUMS. OG treatment effectively improved the depressive-like behaviors of OVX-CUMS mice, as indicated by increased sucrose intake in sucrose preference test (SPT), reduced immobility time in forced swimming test (FST), and tail suspension test (TST), lower frequency of grooming and defecation, increased actions of rearing, and prolonged duration in the center in open field test (OFT). OG treatment alleviated the OVX-CUMS induced dysfunction of hypothalamic-pituitary-ovarian (HPO) axis by increased serum estradiol (E2) and decreased ovarian hormones follicle stimulating hormone (FSH), luteinizing hormone (LH), and gonadotropin-releasing hormone (GnRH) in serum. Meanwhile, OG reversed the hyperactivity of hypothalamic-pituitary-adrenal (HPA) axis as evidenced by decreased CORT and ACTH in serum, reduced as well as the mRNA and protein expression of corticotropin-releasing hormone (CRH) in hypothalamus and hippocampus. Moreover, OG up-regulated the protein expression of BDNF, TrkB, and phosphorylation level of CREB and ERK1/2 in hippocampus. These findings demonstrated that OG improves depressive behaviors of OVX-CUMS mice by modulating of HPO/HPA axis dysfunction, and activating BDNF-TrkB-CREB signaling pathway.

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Section: Discussionsupporting

confidence: 91%

Orcinol glucoside improves the depressive‐like behaviors of perimenopausal depression mice through modulating activity of hypothalamic–pituitary–adrenal/ovary axis and activating BDNF‐ TrkB‐CREB signaling pathway

Zhang

et al. 2021

Phytotherapy Research

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“…In our study, Nsun5 KO decreased the protein level of GCLM in the mouse ovary, which suggests that deletion of Nsun5 accelerated oxidative DNA damage in oocytes by elevating the level of oxidative damage. Our results support adding FSH to the culture system of granulosa cells and neuroblastoma cells to elevate the protein expression of GCLM 30 …”

Section: Discussionsupporting

confidence: 76%

“…Our results support adding FSH to the culture system of granulosa cells and neuroblastoma cells to elevate the protein expression of GCLM. 30 …”

Section: Discussionmentioning

confidence: 99%

RNA‐methyltransferase Nsun5 controls the maternal‐to‐zygotic transition by regulating maternal mRNA stability

Ding

et al. 2022

Clinical & Translational Med

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Background RNA modification‐induced ovarian dysgenesis appears to be necessary for ovary development. However, how m 5 C (5‐methylcytosine)‐coordinating modificatory transcripts are dynamically regulated during oogenesis, and ovarian development is unknown. The purpose of this study was to determine whether NOP2/Sun RNA methyltransferase 5 (Nsun5) deletion leads to suppression of ovarian function and arrest of embryonic development. The regulation of mRNA decay and stability by m 5 C modification is essential at multiple stages during the maternal‐to‐zygotic (MZT) transition. Methods Mouse ovaries and oocytes with Nsun5 KO and the KGN cell line were subjected to m 5 C identification, alternative splicing analysis and protein expression. BS‐m 5 C‐seq, real‐time polymerase chain reaction, Western blot, immunofluorescence and actinomycin D treatment assays were used. In particular, BS‐m 5 C‐seq revealed a dynamic pattern of m 5 C sites and genes in the ovaries between Nsun5 KO and WT mice at the 2‐month and 6‐month stages. Diverse bioinformatic tools were employed to identify target genes for Nsun5. Results Here, a maternal mRNA stability study showed that deletion of the m 5 C methyltransferase Nsun5 obstructs follicular development and ovarian function, which leads directly to inhibition of embryogenesis and embryo development. Dynamic analysis of m 5 C revealed that the level of m 5 C decreased in a time‐dependent manner after Nsun5 knockout. Regarding the molecular mechanism, we found that Nsun5 deficiency caused a m 5 C decline in the exon and 3′UTR regions that influenced the translation efficiency of Mitotic arrest deficient 2 like 2 (MAD2L2) and Growth differentiation factor 9 (GDF9) in the ovary. Mechanistic investigation of alternative splicing indicated that Nsun5 KO triggers aberrant events in the exon region of Brd8 . Conclusions Nsun5 loss arrests follicular genesis and development in ovarian aging, indicating that Nsun5/m 5 C‐regulated maternal mRNA stabilization is essential for MZT transition.

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“…Impairment of the antioxidant system in the brain exacerbates depressive symptoms, and increased oxidative stress has been observed previously in CUMS models [ 27 , 28 ]. Furthermore, ROS have also been shown to trigger activation of the NLRP3 inflammasome [ 29 ].…”

Section: Discussionmentioning

confidence: 80%

Polysaccharides from Polygonatum cyrtonema Hua Reduce Depression-Like Behavior in Mice by Inhibiting Oxidative Stress-Calpain-1-NLRP3 Signaling Axis

Shen

Xie

et al. 2022

Oxidative Medicine and Cellular Longevity

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Polysaccharides from Polygonatum cyrtonema Hua (PSP) exert antioxidant, anti-inflammatory, and antidepressant effects. Production of reactive oxygen species (ROS) and activation of the calpain system and the NOD-like receptor protein 3 (NLRP3) inflammasome are closely related to the pathogenesis of depression. However, the relationships among those pathways and the protective effects of PSP have not been characterized. In this study, lipopolysaccharide (LPS) and chronic unpredictable mild stress- (CUMS-) induced depression models were used to evaluate the protective mechanisms of PSP against depression. ROS levels were measured in HT-22 cells using flow cytometry. Brain tissues were collected to determine the levels of oxidation-related indicators and inflammatory cytokines. The protein levels of calpain-1, calpain-2, calpastatin, phosphatase and Tensin Homolog deleted on Chromosome 10 (PTEN), suprachiasmatic nucleus circadian oscillatory protein (SCOP), nuclear factor-erythroid factor 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), NLRP3, apoptosis-associated speck-like protein (ASC), caspase-1, cleaved-caspase-1, ionized calcium binding adapter molecule 1 (Iba1), phosphorylation of extracellular signal-regulated kinase (p-ERK), nuclear factor-kappa B (NF-κB), interleukin-1β (IL-1β), and glial fibrillary acidic protein (GFAP) were measured using western blotting or immunofluorescence. In cellular experiments, we showed that PSP attenuated LPS-induced production of ROS in HT-22 cells. In animal experiments, we found that LPS increased the expression of calpain-1, NLRP3, ASC, caspase-1, cleaved-caspase-1, Iba1, p-ERK, NF-κB, and GFAP and reduced the expression of calpastatin, PTEN, SCOP, and Nrf2. Administration of PSP reversed these changes. N-Acetyl-L-cysteine (NAC) administration also inhibited oxidative stress and activation of the calpain system and the NLRP3 inflammasome. Furthermore, PSP, calpeptin, MCC950 (a selective NLRP3 inflammasome inhibitor), and NAC reduced LPS-induced proinflammatory cytokine release. We also showed that PSP prevented CUMS-induced changes in the calpain system and the Nrf2 and NLRP3 signaling pathways and reduced depression-like behavior. These results indicate that PSP exerts antidepressant effects through regulation of the oxidative stress-calpain-1-NLRP3 signaling axis.

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FSHR ablation induces depression-like behaviors

Cited by 14 publications

References 44 publications

Orcinol glucoside improves the depressive‐like behaviors of perimenopausal depression mice through modulating activity of hypothalamic–pituitary–adrenal/ovary axis and activating BDNF‐ TrkB‐CREB signaling pathway

Orcinol glucoside improves the depressive‐like behaviors of perimenopausal depression mice through modulating activity of hypothalamic–pituitary–adrenal/ovary axis and activating BDNF‐ TrkB‐CREB signaling pathway

RNA‐methyltransferase Nsun5 controls the maternal‐to‐zygotic transition by regulating maternal mRNA stability

Polysaccharides from Polygonatum cyrtonema Hua Reduce Depression-Like Behavior in Mice by Inhibiting Oxidative Stress-Calpain-1-NLRP3 Signaling Axis

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