共查询到20条相似文献,搜索用时 15 毫秒
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Understanding the effects to human health resulting from exposure to low doses of ionizing radiation is a persisting challenge. No one questions the deleterious consequences for humans following exposure to high radiation doses; however, in the low dose range, the complex and to some extent unknown cellular responses raise important misgivings about the resulting protective or potentially detrimental effects. Bystander effects are involved in low dose exposures, being characterized by the appearance in unirradiated cells of a cellular damage associated with direct radiation exposure. The purpose of our work was to assess, by using clonogenic and micronuclei assays, the dose and time dependence of the bystander response after cells exposure to very low doses of α-particles and to evaluate its importance in the overall induced damage. The study includes an irradiated cells culture, a medium transfer culture with non-irradiated cells and a culture with irradiated cells after centrifugation. We observed a non-negligible contribution of the bystander effects in the overall cellular damage. Low-dose hyper-sensitivity was observed for medium transfer and irradiated cells after centrifugation cultures. Delayed and earlier cellular damage were similar in almost all experiments, suggesting an effectiveness of irradiated medium to induce a bystander response soon after irradiation. 相似文献
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Mei Jing Piao Ki Cheon Kim Sungwook Chae Young Sam Keum Hye Sun Kim Jin Won Hyun 《Biomolecules & therapeutics.》2013,21(3):210-215
Ionizing radiation can induce cellular oxidative stress through the generation of reactive oxygen species, resulting in cell damage and cell death. The aim of this study was to determine whether the antioxidant effects of the flavonoid fisetin (3,7,3'',4''-tetrahydroxyflavone) included the radioprotection of cells exposed to γ-irradiation. Fisetin reduced the levels of intracellular reactive oxygen species generated by γ-irradiation and thereby protected cells against γ-irradiation-induced membrane lipid peroxidation, DNA damage, and protein carbonylation. In addition, fisetin maintained the viability of irradiated cells by partially inhibiting γ-irradiation-induced apoptosis and restoring mitochondrial membrane potential. These effects suggest that the cellular protective effects of fisetin against γ-irradiation are mainly due to its inhibition of reactive oxygen species generation. 相似文献
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There is growing evidence that the radiation effects at low doses are not adequately described by a simple linear extrapolation from high doses, due, among others, to bystander effects. Though several studies have been published on this topic, the explanation of the mechanisms describing the bystander effects remains unclear. This study aims at understanding how the bystander signals are or can be propagated in the cell culture, namely if the number of irradiated cells influences the bystander response. An A549 cell line was exposed to several doses of α-particles, being the bystander response quantified in two non-irradiated areas. The radius of irradiated areas differs by a factor of 2, and the non-irradiated areas were optimally designed to have the same number of cells. Our results show evidence for bystander effects occurring in cells far away from the irradiated ones, meaning that bystander signals can easily spread throughout the cell culture. Additionally, our study highlights that the damage caused by radiation on the surrounding of irradiated areas could be different according to the number of irradiated cells, i.e., for the same dose value; the overall cellular damage could be different. 相似文献
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Ting Gu Wei Yuan Chen Li Zhilong Chen Yuting Wen Qiyi Zheng Qing Yang Xingyao Xiong Anwen Yuan 《Toxins》2021,13(3)
α-Solanine, a bioactive compound mainly found in potato, exhibits anti-cancer activity towards multiple cancer cells. However, its effects on human choriocarcinoma have not been evaluated. In the present study, we investigated the effect of α-solanine on cell proliferation and apoptosis in human choriocarcinoma in vitro and in vivo. The results showed that α-solanine, at concentrations of 30 μM or below, did not affect the cell viability of the choriocarcinoma cell line JEG-3. However, colony formation was significantly decreased and cell apoptosis was increased in response to 30 μM α-solanine. In addition, α-solanine (30 μM) reduced the migration and invasion abilities of JEG-3 cells, which was associated with a downregulation of matrix metalloproteinases (MMP)-2/9. The in vivo findings provided further evidence of the inhibition of α-solanine on choriocarcinoma tumor growth. α-Solanine suppressed the xenograft tumor growth of JEG-3 cells, resulting in smaller tumor volumes and lower tumor weights. Apoptosis was promoted in xenograft tumors of α-solanine-treated mice. Moreover, α-solanine downregulated proliferative cellular nuclear antigen (PCNA) and Bcl-2 levels and promoted the expression of Bax. Collectively, α-solanine inhibits the growth, migration, and invasion of human JEG-3 choriocarcinoma cells, which may be associated with the induction of apoptosis. 相似文献
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I Dal Prà A Chiarini R Pacchiana E Gardenal B Chakravarthy J. F Whitfield U Armato 《Current Neuropharmacology》2014,12(4):353-364
It is generally assumed that the neuropathology of sporadic (late-onset or nonfamilial) Alzheimer’s disease (AD) is driven by the overproduction and spreading of first Amyloid-βx-42 (Aβ42) and later hyperphosphorylated (hp)-Tau oligomeric “infectious seeds”. Hitherto, only neurons were held to make and spread both oligomer types; astrocytes would just remove debris. However, we have recently shown that exogenous fibrillar or soluble Aβ peptides specifically bind and activate the Ca2+-sensing receptors (CaSRs) of untransformed human cortical adult astrocytes and postnatal neurons cultured in vitro driving them to produce, accrue, and secrete surplus endogenous Aβ42. While the Aβ-exposed neurons start dying, astrocytes survive and keep oversecreting Aβ42, nitric oxide (NO), and vascular endothelial growth factor (VEGF)-A. Thus astrocytes help neurons’ demise. Moreover, we have found that a highly selective allosteric CaSR agonist (“calcimimetic”), NPS R-568, mimics the just mentioned neurotoxic actions triggered by Aβ●CaSR signaling. Contrariwise, and most important, NPS 2143, a highly selective allosteric CaSR antagonist (“calcilytic”), fully suppresses all the Aβ●CaSR signaling-driven noxious actions. Altogether our findings suggest that the progression of AD neuropathology is promoted by unceasingly repeating cycles of accruing exogenous Aβ42 oligomers interacting with the CaSRs of swelling numbers of astrocyte-neuron teams thereby recruiting them to overrelease additional Aβ42 oligomers, VEGF-A, and NO. Calcilytics would beneficially break such Aβ/CaSR-driven vicious cycles and hence halt or at least slow the otherwise unstoppable spreading of AD neuropathology 相似文献
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Luiz Keller Luís Abrunhosa Kelly Keller Carlos Alberto Rosa Lilia Cavaglieri Armando Venancio 《Toxins》2015,7(8):3297-3308
Zearalenone (ZEA) and its derivatives are mycotoxins with estrogenic effects on mammals. The biotransformation for ZEA in animals involves the formation of two major metabolites, α- and β-zearalenol (α-ZOL and β-ZOL), which are subsequently conjugated with glucuronic acid. The capability of Saccharomyces cerevisiae strains isolated from silage to eliminate ZEA and its derivatives α-ZOL and β-ZOL was investigated as, also, the mechanisms involved. Strains were grown on Yeast Extract-Peptone-Dextrose medium supplemented with the mycotoxins and their elimination from medium was quantified over time by HPLC-FL. A significant effect on the concentration of ZEA was observed, as all the tested strains were able to eliminate more than 90% of the mycotoxin from the culture medium in two days. The observed elimination was mainly due to ZEA biotransformation into β-ZOL (53%) and α-ZOL (8%) rather than to its adsorption to yeast cells walls. Further, the biotransformation of α-ZOL was not observed but a small amount of β-ZOL (6%) disappeared from culture medium. ZEA biotransformation by yeasts may not be regarded as a full detoxification process because both main end-products are still estrogenic. Nonetheless, it was observed that the biotransformation favors the formation of β-ZOL which is less estrogenic than ZEA and α-ZOL. This metabolic effect is only possible if active strains are used as feed additives and may play a role in the detoxification performance of products with viable S. cerevisiae cells. 相似文献
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Ming-cheng Yu Feng Yang Xiao-yu Ding Nan-nan Sun Zheng-yuan Jiang Ya-fei Huang Yu-rong Yan Chen Zhu Qiong Xie Zhi-feng Chen Si-qi Guo Hua-liang Jiang Kai-xian Chen Cheng Luo Xiao-min Luo Shi-jie Chen Yong-hui Wang 《Acta pharmacologica Sinica》2021,42(9):1524
A series of 6-substituted carbazole-based retinoic acid-related orphan receptor gamma-t (RORγt) modulators were discovered through 6-position modification guided by insights from the crystallographic profiles of the “short” inverse agonist 6. With the increase in the size of the 6-position substituents, the “short” inverse agonist 6 first reversed its function to agonists and then to “long” inverse agonists. The cocrystal structures of RORγt complexed with the representative “short” inverse agonist 6 (PDB: 6LOB), the agonist 7d (PDB: 6LOA) and the “long” inverse agonist 7h (PDB: 6LO9) were revealed by X-ray analysis. However, minor differences were found in the binding modes of “short” inverse agonist 6 and “long” inverse agonist 7h. To further reveal the molecular mechanisms of different RORγt inverse agonists, we performed molecular dynamics simulations and found that “short” or “long” inverse agonists led to different behaviors of helixes H11, H11’, and H12 of RORγt. The “short” inverse agonist 6 destabilizes H11’ and dislocates H12, while the “long” inverse agonist 7h separates H11 and unwinds H12. The results indicate that the two types of inverse agonists may behave differently in downstream signaling, which may help identify novel inverse agonists with different regulatory mechanisms. 相似文献
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Ye-Seul Yoon Woo Jung Ahn Diadem Ricarte Darlene Ortiz Chan Young Shin Seung-Jae Lee He-Jin Lee 《Biomolecules & therapeutics.》2021,29(1):83
Multiple system atrophy (MSA) is a neurodegenerative disease characterized by presence of α-synuclein-positive inclusions in the cytoplasm of oligodendrocytes. These glial cytoplasmic inclusions (GCIs) are considered an integral part of the pathogenesis of MSA, leading to demyelination and neuronal demise. What is most puzzling in the research fields of GCIs is the origin of α-synuclein aggregates in GCIs, since adult oligodendrocytes do not express high levels of α-synuclein. The most recent leading hypothesis is that GCIs form via transfer and accumulation of α-synuclein from neurons to oligodendrocytes. However, studies regarding this subject are limited due to the absence of proper human cell models, to demonstrate the entry and accumulation of neuronal α-synuclein in human oligodendrocytes. Here, we generated mature human oligodendrocytes that can take up neuron-derived α-synuclein and form GCI-like inclusions. Mature human oligodendrocytes are derived from neural stem cells via “oligosphere” formation and then into oligodendrocytes, treating the cells with the proper differentiation factors at each step. In the final cell preparations, oligodendrocytes consist of the majority population, while some astrocytes and unidentified stem cell-like cells were present as well. When these cells were exposed to α-synuclein proteins secreted from neuron-like human neuroblastoma cells, oligodendrocytes developed perinuclear inclusion bodies with α-synuclein immunoreactivity, resembling GCIs, while the stem cell-like cells showed α-synuclein-positive, scattered puncta in the cytoplasm. In conclusion, we have established a human oligodendrocyte model for the study of GCI formation, and the characterization and use of this model might pave the way for understanding the pathogenesis of MSA. 相似文献
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Manuela B. Pucca Felipe A. Cerni Steve Peigneur Karla C. F. Bordon Jan Tytgat Eliane C. Arantes 《Toxins》2015,7(7):2534-2550
The toxin, previously described as a “non-toxic” toxin, was isolated from the scorpion venom of Tityus serrulatus (Ts), responsible for the most severe and the highest number of accidents in Brazil. In this study, the subtype specificity and selectivity of Ts4 was investigated using six mammalian Nav channels (Nav1.2→Nav1.6 and Nav1.8) and two insect Nav channels (DmNav1 and BgNav). The electrophysiological assays showed that Ts4 specifically inhibited the fast inactivation of Nav1.6 channels, the most abundant sodium channel expressed in the adult central nervous system, and can no longer be classified as a “non-toxic peptide”. Based on the results, we could classify the Ts4 as a classical α-toxin. The Ts4 3D-structural model was built based on the solved X-ray Ts1 3D-structure, the major toxin from Ts venom with which it shares high sequence identity (65.57%). The Ts4 model revealed a flattened triangular shape constituted by three-stranded antiparallel β-sheet and one α-helix stabilized by four disulfide bonds. The absence of a Lys in the first amino acid residue of the N-terminal of Ts4 is probably the main responsible for its low toxicity. Other key amino acid residues important to the toxicity of α- and β-toxins are discussed here. 相似文献
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Carmel Mothersill Richard Smith Matthew Henry Colin Seymour Raimond Wong 《Dose-response》2013,11(1):82-98
Many so-called “alternative medicine” techniques such as Reiki and acupuncture produce very good outcomes for intractable pain and other chronic illnesses but the efficacy is often dismissed as being psychosomatic. However a plausible mechanism does exist i.e. that the treatments alter the electromagnetic fields in living organisms and thereby prevent or reduce activity of neurons which lead to the pain. Low doses of ionising radiation have similar effects on electromagnetic fields and are known to induce signaling cascades in tissues due to ion gradients. To test this hypothesis cell cultures were exposed to Reiki – like and to acupuncture – like treatments, both performed by qualified practitioners. The cells were exposed either before or after the treatment to x-rays and were monitored for production of direct damage or bystander signals. The data suggest that the alternative techniques altered the response of cells to direct irradiation and altered bystander signal mechanisms. We conclude that alternative medicine techniques involving electromagnetic perturbations may modify the response of cells to ionizing radiation. In addition to the obvious implications for mechanistic studies of low dose effects, this could provide a novel target to exploit in radiation protection and in optimizing therapeutic gain during radiotherapy. 相似文献
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Xiao-ke Ji Yuan-kang Xie Jun-qiao Zhong Qi-gang Xu Qi-qiang Zeng Yang Wang Qi-yu Zhang Yun-feng Shan 《Acta pharmacologica Sinica》2015,36(3):334-342
Aim:
Glycogen synthase kinase 3β (GSK-3β) plays a crucial role in hepatic biology, including liver development, regeneration, proliferation and carcinogenesis. In this study we investigated the role of GSK-3β in regulation of growth of hepatic oval cells in vitro and in liver regeneration in partially hepatectomized rats.Methods:
WB-F344 cells, the rat hepatic stem-like epithelial cells, were used as representative of oval cells. Cell viability was examined using a WST-8 assay. The cells were transfected with a recombinant lentivirus expressing siRNA against GSK-3β (GSK-3βRNAiLV) or a lentivirus that overexpressed GSK-3β (GC-GSK-3βLV). Adult rats underwent partial (70%) hepatectomy, and liver weight and femur length were measured at d 7 after the surgery. The expression of GSK-3β, phospho-Ser9-GSK-3β, β-catenin and cyclin D1 was examined with immunoblotting assays or immunohistochemistry.Results:
Treatment of WB-F344 cells with the GSK-3β inhibitor SB216763 (5 and 10 μmol/L) dose-dependently increased the levels of phospho-Ser9-GSK-3β, but not the levels of total GSK-3β, and promoted the cell proliferation. Knockout of GSK-3β with GSK-3βRNAiLV increased the cell proliferation, whereas overexpression of GSK-3β with GC-GSK-3βLV decreased the proliferation. Both SB216763 and GSK-3βRNAiLV significantly increased the levels of β-catenin and cyclin D1 in the cells, whereas GSK-3β overexpression decreased their levels. In rats with a partial hepatectomy, administration of SB216763 (2 mg/kg, ip) significantly increased the number of oval cells, the levels of phospho-Ser9-GSK-3β, β-catenin and cyclin D1 in liver, as well as the ratio of liver weight to femur length at d 7 after the surgery.Conclusion:
GSK-3β suppresses the proliferation of hepatic oval cells by modulating the Wnt/β-catenin signaling pathway. 相似文献13.
Jun Li Shu-zhi Zhao Pei-pei Wang Song-ping Yu Zhi Zheng Xun Xu 《Acta pharmacologica Sinica》2012,33(8):1030-1036
Aim:
To investigate the effects of high glucose (HG) medium on expression of hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF) in cultured rat retinal Müller cells and to determine the signaling pathways mediating the effects.Methods:
Primary cultures of retinal Müller cells were prepared from Sprague-Dawley rats, and incubated in a medium containg HG (30 mmol/L) in the presence of the membrane-permeable Ca2+ chelator BAPTA-AM (10 μmol/L) or the CaMKII inhibitor KN93 (10 μmol/L). The levels of CaMKII, p-CaMKII, CREB, p-CREB, HIF-1α, and VEGF proteins were measured with Western blotting, while HIF-1á and VEGF mRNA levels were determined using real-time RT-PCR.Results:
The stimulation of retinal Müller cell with HG for 24 h remarkably increased the expression levels of HIF-1α and VEGF. These responses were significantly inhibited in the presence of BAPTA-AM or KN93. Both BAPTA-AM and KN93 also significantly inhibited HG-induced phosphorylation of CaMKII and CREB in the cultured retinal Müller cells. Transfection of the cultured retinal Müller cells with antisense CREB oligonucleotide (300 nmol/L) was similarly effective in blocking the HG-induced increase of HIF-1α and VEGF.Conclusion:
HG-induced HIF-1α and VEGF expression in cultured rat retinal Müller cells depends on intracellular free Ca2+ and activation of CaMKII-CREB pathway. The activation of CaMKII-CREB pathway by HG may be a possible mechanism underlying the pathogenesis of diabetic retinopathy. 相似文献14.
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Hai Yang Yu Sung Ok Kim Cheng-Yun Jin Gi-Young Kim Wun-Jae Kim Young Hyun Yoo Yung Hyun Choi 《Biomolecules & therapeutics.》2014,22(3):184-192
β-lapachone is a naturally occurring quinone that selectively induces apoptotic cell death in a variety of human cancer cells in vitro and in vivo; however, its mechanism of action needs to be further elaborated. In this study, we investigated the effects of β-lapachone on the induction of apoptosis in human gastric carcinoma AGS cells. β-lapachone significantly inhibited cellular proliferation, and some typical apoptotic characteristics such as chromatin condensation and an increase in the population of sub-G1 hypodiploid cells were observed in β-lapachone-treated AGS cells. Treatment with β-lapachone caused mitochondrial transmembrane potential dissipation, stimulated the mitochondria-mediated intrinsic apoptotic pathway, as indicated by caspase-9 activation, cytochrome c release, Bcl-2 downregulation and Bax upregulation, as well as death receptor-mediated extrinsic apoptotic pathway, as indicated by activation of caspase-8 and truncation of Bid. This process was accompanied by activation of caspase-3 and concomitant with cleavage of poly(ADP-ribose) polymerase. The general caspase inhibitor, z-VAD-fmk, significantly abolished β-lapachone-induced cell death and inhibited growth. Further analysis demonstrated that the induction of apoptosis by β-lapachone was accompanied by inactivation of the phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway. The PI3K inhibitor LY29004 significantly increased β-lapachone-induced apoptosis and growth inhibition. Taken together, these findings indicate that the apoptotic activity of β-lapachone is probably regulated by a caspase-dependent cascade through activation of both intrinsic and extrinsic signaling pathways, and that inhibition of the PI3K/Akt signaling may contribute to β-lapachone-mediated AGS cell growth inhibition and apoptosis induction. 相似文献
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Tao Shan Xi-juan Cui Wei Li Wan-run Lin Hong-wei Lu Yi-ming Li Xi Chen Tao Wu 《Acta pharmacologica Sinica》2014,35(8):1065-1073
Aim:
To investigate the anti-tumor effects of α-mangostin, a major xanthone identified in the pericarp of mangosteen (Garcinia mangostana Linn), against human gastric adenocarcinoma cells in vitro, and the mechanisms of the effects.Methods:
Human gastric adenocarcinoma cell lines BGC-823 and SGC-7901 were treated with α-mangostin. The cell viability was measured with MTT assay, and cell apoptosis was examined using flow cytometry and TUNEL assay. The expression of the relevant proteins was detected using Western blot.Results:
Treatment with α-mangostin (3–10 μg/mL) inhibited the viability of both BGC-823 and SGC-7901 cells in dose- and time-manners. Furthermore, α-mangostin (7 μg/mL) time-dependently increased the apoptosis index of the cancer cells, reduced the mitochondrial membrane potential of the cancer cells, and significantly increased the release of cytochrome c and AIF into cytoplasm. Moreover, the α-mangostin treatment markedly suppressed the constitutive Stat3 protein activation, and Stat3-regulated Bcl-xL and Mcl-1 protein levels in the cancer cells.Conclusion:
The anti-tumor effects of α-mangostin against human gastric adenocarcinoma cells in vitro can be partly attributed to blockade of Stat3 signaling pathway. 相似文献18.
Dong Hyeok Kim Hyun-ju Ihn Chaerin Moon Sang-Seok Oh Soojong Park Suk Kim Keun Woo Lee Kwang Dong Kim 《Biomolecules & therapeutics.》2015,23(1):71-76
Peroxisome proliferator-activated receptor gamma (PPARγ) was identified as a cell-intrinsic regulator of Th17 cell differentiation. Th17 cells have been associated with several autoimmune diseases, including experimental autoimmune encephalomyelitis (EAE), inflammatory bowel disease (IBD), and collagen-induced arthritis. In this study, we confirmed PPARγ-mediated inhibition of Th17 cell differentiation and cytokine production at an early stage. Treatment with ciglitazone, a PPARγ ligand, reduced both IL-1β-mediated enhancement of Th17 differentiation and activation of Th17 cells after polarization. For Th17 cell differentiation, we found that ciglitazone-treated cells had a relatively low proliferative activity and produced a lower amount of cytokines, regardless of the presence of IL-1β. The inhibitory activity of ciglitazone might be due to decrease of CCNB1 expression, which regulates the cell cycle in T cells. Hence, we postulate that a pharmaceutical PPARγ activator might be a potent candidate for treatment of Th17-mediated autoimmune disease patients. 相似文献
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Pathogenesis of cholera diarrhea requires cholera toxin (CT)-mediated adenosine diphosphate (ADP)-ribosylation of stimulatory G protein (Gsα) in enterocytes. CT is an AB5 toxin with an inactive CTA1 domain linked via CTA2 to a pentameric receptor-binding B subunit. Allosterically activated CTA1 fragment in complex with NAD+ and GTP-bound ADP-ribosylation factor 6 (ARF6-GTP) differs conformationally from the CTA1 domain in holotoxin. A surface-exposed knob and a short α-helix (formed, respectively, by rearranging “active-site” and “activation” loops in inactive CTA1) and an ADP ribosylating turn-turn (ARTT) motif, all located near the CTA1 catalytic site, were evaluated for possible roles in recognizing Gsα. CT variants with one, two or three alanine substitutions at surface-exposed residues within these CTA1 motifs were tested for assembly into holotoxin and ADP-ribosylating activity against Gsα and diethylamino-(benzylidineamino)-guanidine (DEABAG), a small substrate predicted to fit into the CTA1 active site). Variants with single alanine substitutions at H55, R67, L71, S78, or D109 had nearly wild-type activity with DEABAG but significantly decreased activity with Gsα, suggesting that the corresponding residues in native CTA1 participate in recognizing Gsα. As several variants with multiple substitutions at these positions retained partial activity against Gsα, other residues in CTA1 likely also participate in recognizing Gsα. 相似文献
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Corey Fee Thomas D Prevot Keith Misquitta Daniel E Knutson Guanguan Li Prithu Mondal James M Cook Mounira Banasr Etienne Sibille 《The international journal of neuropsychopharmacology / official scientific journal of the Collegium Internationale Neuropsychopharmacologicum (CINP)》2021,24(6):505
IntroductionDeficits in somatostatin-positive gamma-aminobutyric acid interneurons (SST+ GABA cells) are commonly reported in human studies of mood and anxiety disorder patients. A causal link between SST+ cell dysfunction and symptom-related behaviors has been proposed based on rodent studies showing that chronic stress, a major risk factor for mood and anxiety disorders, induces a low SST+ GABA cellular phenotype across corticolimbic brain regions; that lowering Sst, SST+ cell, or GABA functions induces depressive-/anxiety-like behaviors (a rodent behavioral construct collectively defined as “behavioral emotionality”); and that disinhibiting SST+ cells has antidepressant-like effects. Recent studies found that compounds preferentially potentiating receptors mediating SST+ cell functions, α5-GABAA receptor positive allosteric modulators (α5-PAMs), achieved antidepressant-like effects. Together, the evidence suggests that SST+ cells regulate mood and cognitive functions that are disrupted in mood disorders and that rescuing SST+ cell function via α5-PAM may represent a targeted therapeutic strategy.MethodsWe developed a mouse model allowing chemogenetic manipulation of brain-wide SST+ cells and employed behavioral characterization 30 minutes after repeated acute silencing to identify contributions to symptom-related behaviors. We then assessed whether an α5-PAM, GL-II-73, could rescue behavioral deficits.ResultsBrain-wide SST+ cell silencing induced features of stress-related illnesses, including elevated neuronal activity and plasma corticosterone levels, increased anxiety- and anhedonia-like behaviors, and impaired short-term memory. GL-II-73 led to antidepressant- and anxiolytic-like improvements among behavioral deficits induced by brain-wide SST+ cell silencing.ConclusionOur data validate SST+ cells as regulators of mood and cognitive functions and demonstrate that bypassing low SST+ cell function via α5-PAM represents a targeted therapeutic strategy. 相似文献