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Unraveling the gut-brain axis:the impact of steroid hormones and nutrition on Parkinson's disease

Neural Regeneration Research 2024年第10期19卷 2219-2228页

作者： Paula Maria Neufeld Ralf A.Nettersheim Veronika Matschke Matthias Vorgerd Sarah Stahlke Carsten Theiss Department of Cytology Institute of AnatomyMedical FacultyRuhr-University BochumBochumGermany Department of Visceral Surgery University Hospital BergmannsheilRuhr-University BochumBochumGermany Department of Neurology Heimer Institute for Muscle ResearchUniversity Hospital BergmannsheilRuhr-University BochumBochumGermany

This comprehensive review explores the intricate relationship between nutrition,the gut microbiome,steroid hormones,and Parkinson's disease within the context of the gut-brain axis.The gut-brain axis plays a pivotal role in neurodegenerative diseases like Parkinson's disease,encompassing diverse components such as the gut microbiota,immune system,metabolism,and neural pathways.The gut microbiome,profoundly influenced by dietary factors,emerges as a key player.Nutrition during the first 1000 days of life shapes the gut microbiota composition,influencing immune responses and impacting both child development and adult health.High-fat,high-sugar diets can disrupt this delicate balance,contributing to inflammation and immune dysfunction.Exploring nutritional strategies,the Mediterranean diet's anti-inflammatory and antioxidant properties show promise in reducing Parkinson's disease risk.Microbiome-targeted dietary approaches and the ketogenic diet hold the potential in improving brain disorders.Beyond nutrition,emerging research uncovers potential interactions between steroid hormones,nutrition,and Parkinson's disease.progesterone,with its anti-inflammatory properties and presence in the nervous system,offers a novel option for Parkinson's disease therapy.Its ability to enhance neuroprotection within the enteric nervous system presents exciting prospects.The review addresses the hypothesis thatα-synuclein aggregates originate from the gut and may enter the brain via the vagus nerve.Gastrointestinal symptoms preceding motor symptoms support this hypothesis.Dysfunctional gut-brain signaling during gut dysbiosis contributes to inflammation and neurotransmitter imbalances,emphasizing the potential of microbiota-based interventions.In summary,this review uncovers the complex web of interactions between nutrition,the gut microbiome,steroid hormones,and Parkinson's disease within the gut-brain axis framework.Understanding these connections not only offers novel therapeutic insights but also illuminates the origins of neurode

关键词： diet gut-brain axis microbiome neurodegenerative diseases nutrition Parkinson's disease progesterone steroid hormones

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Effects of progesterone on T-type-Ca^(2+)-channel expression in Purkinje cells

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Neural Regeneration Research 2022年第11期17卷 2465-2471页

作者： Annika Eickhoff Jonas Tjaden Sarah Stahlke Matthias Vorgerd Verena Theis Veronika Matschke Carsten Theiss Department of Cytology Institute of AnatomyRuhr-University BochumBochumGermany Department of Neurology Neuromuscular Center RuhrgebietUniversity Hospital BergmannsheilRuhr-Universität BochumBochumGermany

Plasticity of cerebellar Purkinje cells(PC)is influenced by progeste rone via the classical progeste rone receptors PR-A and PR-B by stimulating dendritogenesis,spinogenesis,and synaptogenesis in these cells.Dissociated PC cultures were used to analyze progeste rone effects at a molecular level on the voltage-gated T-type-Ca^(2+)-channels Ca_(v)3.1,Ca_(v)3.2,and Ca_(v)3.3 as they helped determine neuronal plasticity by regulating Ca^(2+)-influx in neuronal cells.The results showed direct effects of progesterone on the mRNA expression of T-type-Ca^(2+)-channels,as well as on the protein kinases A and C being involved in downstream signaling pathways that play an important role in neuronal plasticity.For the mRNA expression studies of T-type-Ca^(2+)-channels and protein kinases of the signaling cascade,laser microdissection and purified PC cultures of diffe rent maturation stages were used.Immunohistochemical staining was also performed to characte rize the localization of T-type-Ca^(2+)-channels in PC.Expe rimental progesterone treatment was performed on the purified PC culture for 24 and 48 hours.Our results show that progesterone increases the expression of Ca_(v)3.1 and Ca_(v)3.3 and associated protein kinases A and Cin PC at the mRNA level within 48 hours after treatment at latest.These effects extend the current knowledge of the function of progesterone in the central nervous system and provide an explanatory approach for its influence on neuronal plasticity.

关键词： Ca_(v)3.1 Ca_(v)3.2 Ca_(v)3.3 neuronal plasticity progesterone protein kinase A protein kinase C Purkinje cells rat cerebellum T-type-Ca^(2+)-channels

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Modulation of innate immune response to viruses including SARS-CoV-2 by progesterone

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Signal Transduction and Targeted Therapy 2022年第5期7卷 1783-1796页

作者： Shan Su Duo Hua Jin-Peng Li Xia-Nan Zhang Lei Bai Li-Bo Cao Yi Guo Ming Zhang Jia-Zhen Dong Xiao-Wei Liang Ke Lan Ming-Ming Hu Hong-Bing Shu Department of Infectious Diseases Frontier Science Center for Immunology and MetabolismMedical Research InstituteZhongnan Hospital of Wuhan UniversityWuhan UniversityWuhan 430071China Department of Thyroid and Breast Surgery Zhongnan Hospital of Wuhan UniversityWuhan 430071China State Key Laboratory of Virology College of Life SciencesWuhan UniversityWuhan 430071China

Whether and how innate antiviral response is regulated by humoral metabolism remains enigmatic.We show that viral infection induces progesterone via the hypothalamic-pituitary-adrenal axis in mice.progesterone induces downstream antiviral genes and promotes innate antiviral response in cells and mice,whereas knockout of the progesterone receptor PGR has opposite effects.Mechanistically,stimulation of PGR by progesterone activates the tyrosine kinase SRC,which phosphorylates the transcriptional factor IRF3 at Y107.

关键词： progesterone metabolism stimulation

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progesterone in gender-affirming therapy of trans women

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World Journal of Biological Chemistry 2022年第3期13卷 66-71页

作者： Charalampos Milionis Ioannis Ilias Eftychia Koukkou Department of Endocrinology Diabetes and MetabolismElena Venizelou HospitalAthens GR-11521Greece

progesterone is an endogenous steroid hormone with an important role for the physiology of the female reproductive system and the mammary gland.It has additional significant actions in other tissues,such as the cardiovascular system,the central nervous system,and bones.The present article explores potential clinical implications from the addition of bioidentical progesterone to genderaffirming treatment of trans women.For this purpose,it provides an overview of the physiological action of progesterone in target tissues and speculates on possible benefits for gender transitioning.progesterone is expected to exert moderate anti-androgen action through suppression of the hypothalamicpituitary-gonadal axis and inhibition of the conversion of testosterone to dihydrotestosterone.It may also contribute to breast maturation.In the long-term,progesterone could prevent bone loss and protect cardiovascular health.The potential benefits are mainly inferred by extrapolating evidence from biological actions in cisgender women and medical assumptions and hence,clinicians need to be cautious when applying these data into practice.Further research is needed to ascertain the efficacy and safety of progesterone in current hormonal regimens.

关键词： progesterone Transgender persons Breast Human Gender dysphoria

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progesterone treatment before experimental hypoxia-ischemia enhances the expression of glucose transporter proteins GLUT1 and GLUT3 in neonatal rats

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Neuroscience Bulletin 2013年第3期29卷 287-294页

作者： Xinjuan Li Hua Han Ruanling Hou Linyu Wei Guohong Wang Chaokun Li Dongliang Li Department of Physiology and Neurobiology Xinxiang Medical University Department of Ultrasonic Diagnosis Central Hospital of Xinxiang City Henan Key Lab of Biological Psychiatry

progesterone is an efficient candidate for treating stroke and traumatic brain damage. The current study was designed to investigate the effects of pro gesterone on glucose transporter proteins （GLUT1 and GLUT3） during hypoxicischemic injury in a neo natal rat model. We demonstrated strong staining for GLUT1 in the walls of blood vessels and GLUT3 im munoreactivity in hippocampal neurons after hypoxia ischemia. Hypoxiaischemia elevated GLUT1 and GLUT3 at both the mRNA and protein levels in the hippocampus, and pretreatment with progesterone （8 mg/kg） further enhanced their accumulation until 24 h after hypoxicischemic injury. These results showed that progesterone treatment induced the accumula tion of both GLUT1 and GLUT3 transporters, and an energycompensation mechanism may be involved in the neuroprotective effect of progesterone during hy poxicischemic injury after cerebral ischemic attacks.

关键词： hypoxic-ischemic injury progesterone GLUT1 GLUT3 stroke

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progesterone promotes neuronal differentiation of human umbilical cord mesenchymal stem cells in culture conditions that mimic the brain microenvironment

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Neural Regeneration Research 2012年第25期7卷 1925-1930页

作者： Xianying Wang Honghai Wu Gai Xue Yanning Hou Hebei Medical University Shijiazhuang 050017 Hebei Province China The Third Hospital of Hebei Medical University Shijiazhuang 050051 Hebei Province China Bethune Intemational Peace Hospital of Chinese PLA Shijiazhuang 050082 Hebei Province China

In this study, human umbilical cord mesenchymal stem cells from full-term neonates born by vagina delivery were cultured in medium containing 150 mg/mL of brain tissue extracts from Sprague-Dawley rats （to mimic the brain microenvironment）. Immunocytochemical analysis demonstrated that the cells differentiated into neuron-like cells. To evaluate the effects of progesterone as a neurosteroid on the neuronal differentiation of human umbilical cord mesenchymal stem cells, we cultured the cells in medium containing progesterone （0.1, 1, 10 pM） in addition to brain tissue extracts. Reverse transcription-PCR and flow cytometric analysis of neuron specific enolase-positive cells revealed that the percentages of these cells increased significantly following progesterone treatment, with the optimal progesterone concentration for neuron-like differentiation being 1 tJM. These results suggest that progesterone can enhance the neuronal differentiation of human umbilical cord mesenchymal stem cells in culture medium containing brain tissue extracts to mimic the brain microenvironment.

关键词： progesterone mesenchymal stem cells neuron differentiation brain tissue extracts neural regeneration

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progesterone:a universal stimulus for neuronal cells?

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Neural Regeneration Research 2015年第4期10卷 547-549页

作者： Verena Theis Carsten Theiss Department of Cytology Institute of AnatomyMedical FacultyRuhr-University Bochum

progesterone： The sexual hormone progesterone is a mem- ber of the steroid hormone family, and is the most import- ant representative of the gestagenes sub-group. It plays an elementary role in the female menstruation cycle and is essential for the establishment and the maintenance of a pregnancy, however gestagenes like progesterone are also abundant in males. In 1990, the existence of steroids was described in different cells of the central nervous system （CNS）（Baulieu and Robel, 1990）. Up until this point, the effect of sexual hormones on neural cells was rather unknown,

关键词： RNA cell progesterone Figure PNS

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progesterone effects on the oligodendrocyte linage: all roads lead to the progesterone receptor

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Neural Regeneration Research 2019年第12期14卷 2029-2034页

作者： Ignacio Jure Alejandro F. De Nicola Florencia Labombarda Laboratorio de Bioquímica Neuroendocrina Instituto de Biología y Medicina Experimental CONICET Buenos Aires Argentina Departamento de Bioquímica Humana Facultad de Medicina Universidad de Buenos Aires Buenos Aires Argentina

A new role has emerged for progesterone after discovering its potent actions away from reproduction in both the central and the peripheral nervous system. The aim of the present report is to discuss progesterone’s mechanisms of action involved in myelination, remyelination and neuroinflammation. The pivotal role of the classic progesterone receptor is described and evidence is compiled about progesterone’s direct effects on oligodendrocyte linage and its indirect effects on oligodendrocyte precursor cell differentiation by decreasing the neuroinflammatory environment.

关键词： progesterone progesterone receptor oligodendrocyte differentiation myelination remyelination neuroinflammation

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progesterone receptor membrane component 1 as a potential prognostic biomarker for hepatocellular carcinoma

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World Journal of Gastroenterology 2018年第10期24卷 1152-1166页

作者： Hung-Wen Tsai Chung-Liang Ho Shu-Wen Cheng Yih-Jyh Lin Chou-Cheng Chen Pin-Nan Cheng Chia-Jui Yen Ting-Tsung Chang Po-Min Chiang Shih-Huang Chan Cheng-Hsun Ho Shu-Hui Chen Yi-Wen Wang Nan-Haw Chow Jou-Chun Lin Institute of Clinical Medicine National Cheng Kung University Hospital College of Medicine National Cheng Kung University Department of Pathology National Cheng Kung University Hospital College of Medicine National Cheng Kung University Institute of Basic Medical Sciences College of Medicine National Cheng Kung University Center of Infectious Disease and Signaling Research College of Medicine National Cheng Kung University Department of Surgery National Cheng Kung University Hospital College of Medicine National Cheng Kung University Department of Internal Medicine National Cheng Kung University Hospital College of Medicine National Cheng Kung University Department of Statistics College of Management National Cheng Kung University Research Center of Clinical Medicine National Cheng Kung University Hospital College of Medicine National Cheng Kung University Department of Chemistry College of Sciences National Cheng Kung University

AIM To investigate the clinicopathological significance of progesterone receptor membrane component 1(PGRMC1) and PGRMC2 in hepatocellular carcinoma(HCC). METHODS We performed immunohistochemical staining to evaluate the estrogen receptor(ER), progesterone receptor(PR), PGRMC1, and PGRMC2 in a clinical cohort consisting of 89 paired HCC and non-tumor liver samples. We also analyzed HCC data(n = 373) from The Cancer Genome Atlas(TCGA). We correlated the expression status of PGRMC1 and PGRMC2 with clinicopathological indicators and the clinical outcomes of the HCC patients. We knocked down or overexpressed PGRMC1 in HCC cell lines to evaluate its biological significance in HCC cell proliferation, differentiation, migration, and invasion. RESULTS We found that few HCC cases expressed ER(5.6%) and PR(4.5%). In contrast, most HCC cases expressed PGRMC1(89.9%) and PGRMC2(100%). PGRMC1 and PGRMC2 exhibited significantly lower expression in tumor tissue than in non-tumor tissue(P < 0.001). Lower PGRMC1 expression in HCC was significantly associated with higher serum alpha-fetoprotein expression(P = 0.004), poorer tumor differentiation(P = 0.045) and liver capsule penetration(P = 0.038). Low PGRMC1 expression was an independent predictor for worse disease-free survival(P = 0.002, HR = 2.384,CI: 1.377-4.128) in our cases, as well as in the TCGA cohort(P < 0.001, HR = 2.857, CI: 1.781-4.584). The expression of PGRMC2 did not relate to patient outcome. PGRMC1 knockdown promoted a poorly differentiated phenotype and proliferation of HCC cells in vitro, while PGRMC1 overexpression caused the opposite effects.CONCLUSION PGRMC1 is a non-classical hormonal receptor that negatively regulates hepatocarcinogenesis. PGRMC1 down-regulation is associated with progression of HCC and is a poor prognostic indicator.

关键词： progesterone receptor membrane component 1 hormonal receptor proliferation hepatocellular carcinoma prognosis

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Pre-implantation exogenous progesterone and pregnancy in sheep:I.polyamines,nutrient transport,and progestamedins

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Journal of Animal Science and Biotechnology 2021年第3期12卷 935-951页

作者： Emily C.Hoskins Katherine M.Halloran Claire Stenhouse Robyn M.Moses Kathrin A.Dunlap Michael C.Satterfield Heewon Seo Gregory A.Johnson Guoyao Wu Fuller W.Bazer Departments of Animal Science Texas A&M UniversityCollege StationTX 77843-2471USA Veterinary Integrative Biosciences Texas A&M UniversityCollege StationTX 77843USA

Background:Administration of exogenous progesterone(P4)to ewes during the pre-implantation period advances conceptus development and implantation.This study determined effects of exogenous P4 on transport of select nutrients and pathways that enhance conceptus development.Pregnant ewes(n=38)were treated with either 25 mg P4 in 1 mL corn oil(P4,n=18)or 1mL corn oil alone(CO,n=20)from day 1.5 through day 8 of pregnancy and hysterectomized on either day 9 or day 12 of pregnancy.Endometrial expression of genes encoding enzymes for synthesis of polyamines,transporters of glucose,arginine,and glycine,as well as progestamedins was determined by RT-qPCR.Results:On day 12 of pregnancy,conceptuses from P4-treated ewes had elongated while those from CO-treated ewes were spherical.The mRNA expression of AZIN2,an arginine decarboxylase,was lower in endometria of P4-treated than CO-treated ewes on day 9 of pregnancy.Expression of FGF10,a progestamedin,was greater in endometria of CO and P4-treated ewes on day 12 of gestation in addition to P4-treated ewes necropsied on day 9 of gestation.Treatment with P4 down-regulated endometrial expression of amino acid transporter SLC1A4 on day 12 of pregnancy.Conclusions:Results indicated that administration of exogenous P4 during the pre-implantation period advanced the expression of FGF10,which may accelerate proliferation of trophectoderm cells,but also was correlated with decreased expression of glycine and serine transporters and polyamine synthesis enzyme AZIN2.Further research with increased sample sizes may determine how differential expression affects endometrial functions and potentially embryonic loss.

关键词： Amino acid Endometrium Gene expression Polyamine progesterone

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