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 pivot...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 neurodegenerative diseases such as Parkinson's disease.展开更多
Impaired axonal transport has been observed in patients with amyotrophic lateral sclerosis(ALS)and in animal models,suggesting that transport proteins likely play a critical role in the pathological mechanism of ALS.D...Impaired axonal transport has been observed in patients with amyotrophic lateral sclerosis(ALS)and in animal models,suggesting that transport proteins likely play a critical role in the pathological mechanism of ALS.Dysregulation of Kinesin-family-member 5α(Kif5α),a neuron-specific isoform of heavy chain kinesin family,has been described in several neurological disorders,in humans and animal models,including ALS.In this study,we determined Kif5αexpression by gene sequencing,quantitative reverse transcription-polymerase chain reaction,and western blot assay in the cervical spinal cord of wobbler mice and immunofluorescence staining in dissociated cultures of the ventral horn.Further,we observed the distribution of Kif5αand mitochondria along motor neuronal branches by confocal imaging.Our results showed that Kif5αexpression was greatly dysregulated in wobbler mice,which resulted in altered distribution of Kif5αalong motor neuronal branches with an abnormal mitochondrial distribution.Thus,our results indicate that dysregulation of Kif5 and therefore abnormal transport in motor neuronal branches in this ALS model could be causative for several pathological findings at the cellular level,like misallocation of cytoskeletal proteins or organelles like mitochondria.展开更多
Oxygen is essential to the human life and life of all aerobic organisms. The complete oxidation of nutrients for the biological energy supply is one of the most important prerequisites for the formation of higher life...Oxygen is essential to the human life and life of all aerobic organisms. The complete oxidation of nutrients for the biological energy supply is one of the most important prerequisites for the formation of higher life forms. However, cells that benefit from oxidative respiration also suffer from reactive oxygen species because they adapted to oxygen as an energy source. Healthy cells balance the formation and elimination of reactive oxygen species thereby creating and keeping reactive oxygen species-homeostasis. When the concentration of free radicals exceeds a critical level and homeostasis is disturbed, oxidative stress occurs leading to damage of multiple cellular molecules and compartments. Therefore, oxidative stress plays an important role in the physiology and pathology of various diseases. Often, the antioxidant protection system becomes pathologically unbalanced in the genesis of several diseases, leading to functional losses of the organism, as in the case of amyotrophic lateral sclerosis, or cells develop metabolic mechanisms to use this system as protection against external influences, such as in the case of glioblastoma cells. Either way, understanding the underlying deregulated mechanisms of the oxidative protection system would allow the development of novel treatment strategies for various diseases. Thus, regardless of the direction in which the reactive oxygen species-homeostasis disequilibrate, the focus should be on the oxidative protection system.展开更多
Vascular endothelial growth factor(VEGF)in neurodevelopment and regeneration:VEGF is a well-known factor that promotes vascularization and angiogenesis.Besides this it participates in the pathogenesis of several disea...Vascular endothelial growth factor(VEGF)in neurodevelopment and regeneration:VEGF is a well-known factor that promotes vascularization and angiogenesis.Besides this it participates in the pathogenesis of several diseases,such as colorectal carcinoma,lung cancer or diabetic retinopathy.Within the last decade,VEGF has been successfully integrated into the treatment of such diseases,for example as a therapy for colorectal cancer with the展开更多
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.Dissociat...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.展开更多
Glioblastoma multiforme(GBM) is a highly aggressive glial brain tumor with an unfavorable prognosis despite all current therapies including surgery, radiation and chemotherapy. One characteristic of this tumor is a st...Glioblastoma multiforme(GBM) is a highly aggressive glial brain tumor with an unfavorable prognosis despite all current therapies including surgery, radiation and chemotherapy. One characteristic of this tumor is a strong synthesis of vascular endothelial growth factor(VEGF), an angiogenesis factor, followed by pronounced vascularization. VEGF became a target in the treatment of GBM, for example with bevacizumab or the tyrosine kinase inhibitor axitinib, which blocks VEGF receptors. To improve patients' prognosis, new targets in the treatment of GBM are under investigations. The role of gap junctions in GBM remains unknown, but some experimental therapies affect these intercellular channels to treat the tumor. Gap junctions are composed of connexins to allow the transport of small molecules between adjacent cells through gap junctional intercellular communication(GJIC). Based on data derived from astrocytes in former studies, which show that VEGF is able to enhance GJIC, the current study analyzed the effects of VEGF, radiation therapy and VEGF receptor blockade by axitinib on GJIC in human GBM cell lines U-87 and U-251. While VEGF is able to induce GJIC in U-251 cells but not in U-87 cells, radiation enhances GJIC in both cell lines. VEGF receptor blockade by axitinib diminishes radiation induced effects in U-251 partially, while increases GJIC in U-87 cells. Our data indicate that VEGF and radiation are both modifying components of GJIC in pathologic brain tumor tissue.展开更多
Progesterone:The sexual hormone progesterone is a member of the steroid hormone family,and is the most important representative of the gestagenes sub-group.It plays an elementary role in the female menstruation cycle ...Progesterone:The sexual hormone progesterone is a member of the steroid hormone family,and is the most important 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展开更多
One of the major challenges in emergency medicine is out-of-hospital cardiac arrest(OHCA).Every year,about 53–62/100000 people worldwide suffer an out-of-hospital cardiac arrest with serious consequences,whereas pers...One of the major challenges in emergency medicine is out-of-hospital cardiac arrest(OHCA).Every year,about 53–62/100000 people worldwide suffer an out-of-hospital cardiac arrest with serious consequences,whereas persistent brain injury is a major cause of morbidity and mortality of those surviving a cardiac arrest.Today,only few and insufficient strategies are known to limit neurological damage of ischemia and reperfusion injury.The aim of the present study was to investigate whether teriflunomide,an approved drug for treatment of relapsing-remitting-multiple-sclerosis,exerts a protective effect on brain cells in an in vitro model of ischemia.Therefore,organotypic slice cultures from rat hippocampus and cerebellum were exposed to oxygen-glucose-deprivation and subsequently treated with teriflunomide.The administration of teriflunomide in the reperfusion time on both hippocampal and cerebellar slice cultures significantly decreased the amount of detectable propidium iodide signal compared with an untreated culture,indicating that more cells survive after oxygen-glucosedeprivation.However,hippocampal slice cultures showed a higher vulnerability to ischemic conditions and a more sensitive response to teriflunomide compared with cerebellar slice cultures.Our study suggests that teriflunomide,applied as a post-treatment after an oxygenglucose-deprivation,has a protective effect on hippocampal and cerebellar cells in organotypic slice cultures of rats.All procedures were conducted under established standards of the German federal state of North Rhine Westphalia,in accordance with the European Communities Council Directive 2010/63/EU on the protection of animals used for scientific purposes.展开更多
The nervous system is a highly complex organization composed of its basicunit,the neuronal cells,and specialized supporting cells,the glial cells.The main glial cells in the central nervous system(CNS)are astrocytes,m...The nervous system is a highly complex organization composed of its basicunit,the neuronal cells,and specialized supporting cells,the glial cells.The main glial cells in the central nervous system(CNS)are astrocytes,microglia and oligodendrocytes.Astrocytes are the most abundant glial cell type in the CNS.展开更多
文摘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 neurodegenerative diseases such as Parkinson's disease.
基金supported by FoRUM–F976-20 (Ruhr-University Bochum)(to VM and CT)
文摘Impaired axonal transport has been observed in patients with amyotrophic lateral sclerosis(ALS)and in animal models,suggesting that transport proteins likely play a critical role in the pathological mechanism of ALS.Dysregulation of Kinesin-family-member 5α(Kif5α),a neuron-specific isoform of heavy chain kinesin family,has been described in several neurological disorders,in humans and animal models,including ALS.In this study,we determined Kif5αexpression by gene sequencing,quantitative reverse transcription-polymerase chain reaction,and western blot assay in the cervical spinal cord of wobbler mice and immunofluorescence staining in dissociated cultures of the ventral horn.Further,we observed the distribution of Kif5αand mitochondria along motor neuronal branches by confocal imaging.Our results showed that Kif5αexpression was greatly dysregulated in wobbler mice,which resulted in altered distribution of Kif5αalong motor neuronal branches with an abnormal mitochondrial distribution.Thus,our results indicate that dysregulation of Kif5 and therefore abnormal transport in motor neuronal branches in this ALS model could be causative for several pathological findings at the cellular level,like misallocation of cytoskeletal proteins or organelles like mitochondria.
文摘Oxygen is essential to the human life and life of all aerobic organisms. The complete oxidation of nutrients for the biological energy supply is one of the most important prerequisites for the formation of higher life forms. However, cells that benefit from oxidative respiration also suffer from reactive oxygen species because they adapted to oxygen as an energy source. Healthy cells balance the formation and elimination of reactive oxygen species thereby creating and keeping reactive oxygen species-homeostasis. When the concentration of free radicals exceeds a critical level and homeostasis is disturbed, oxidative stress occurs leading to damage of multiple cellular molecules and compartments. Therefore, oxidative stress plays an important role in the physiology and pathology of various diseases. Often, the antioxidant protection system becomes pathologically unbalanced in the genesis of several diseases, leading to functional losses of the organism, as in the case of amyotrophic lateral sclerosis, or cells develop metabolic mechanisms to use this system as protection against external influences, such as in the case of glioblastoma cells. Either way, understanding the underlying deregulated mechanisms of the oxidative protection system would allow the development of novel treatment strategies for various diseases. Thus, regardless of the direction in which the reactive oxygen species-homeostasis disequilibrate, the focus should be on the oxidative protection system.
基金the Heinrich and Alma Vogelsang Foundation for financial support in the form of a graduation scholarship
文摘Vascular endothelial growth factor(VEGF)in neurodevelopment and regeneration:VEGF is a well-known factor that promotes vascularization and angiogenesis.Besides this it participates in the pathogenesis of several diseases,such as colorectal carcinoma,lung cancer or diabetic retinopathy.Within the last decade,VEGF has been successfully integrated into the treatment of such diseases,for example as a therapy for colorectal cancer with the
文摘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.
文摘Glioblastoma multiforme(GBM) is a highly aggressive glial brain tumor with an unfavorable prognosis despite all current therapies including surgery, radiation and chemotherapy. One characteristic of this tumor is a strong synthesis of vascular endothelial growth factor(VEGF), an angiogenesis factor, followed by pronounced vascularization. VEGF became a target in the treatment of GBM, for example with bevacizumab or the tyrosine kinase inhibitor axitinib, which blocks VEGF receptors. To improve patients' prognosis, new targets in the treatment of GBM are under investigations. The role of gap junctions in GBM remains unknown, but some experimental therapies affect these intercellular channels to treat the tumor. Gap junctions are composed of connexins to allow the transport of small molecules between adjacent cells through gap junctional intercellular communication(GJIC). Based on data derived from astrocytes in former studies, which show that VEGF is able to enhance GJIC, the current study analyzed the effects of VEGF, radiation therapy and VEGF receptor blockade by axitinib on GJIC in human GBM cell lines U-87 and U-251. While VEGF is able to induce GJIC in U-251 cells but not in U-87 cells, radiation enhances GJIC in both cell lines. VEGF receptor blockade by axitinib diminishes radiation induced effects in U-251 partially, while increases GJIC in U-87 cells. Our data indicate that VEGF and radiation are both modifying components of GJIC in pathologic brain tumor tissue.
文摘Progesterone:The sexual hormone progesterone is a member of the steroid hormone family,and is the most important 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
文摘One of the major challenges in emergency medicine is out-of-hospital cardiac arrest(OHCA).Every year,about 53–62/100000 people worldwide suffer an out-of-hospital cardiac arrest with serious consequences,whereas persistent brain injury is a major cause of morbidity and mortality of those surviving a cardiac arrest.Today,only few and insufficient strategies are known to limit neurological damage of ischemia and reperfusion injury.The aim of the present study was to investigate whether teriflunomide,an approved drug for treatment of relapsing-remitting-multiple-sclerosis,exerts a protective effect on brain cells in an in vitro model of ischemia.Therefore,organotypic slice cultures from rat hippocampus and cerebellum were exposed to oxygen-glucose-deprivation and subsequently treated with teriflunomide.The administration of teriflunomide in the reperfusion time on both hippocampal and cerebellar slice cultures significantly decreased the amount of detectable propidium iodide signal compared with an untreated culture,indicating that more cells survive after oxygen-glucosedeprivation.However,hippocampal slice cultures showed a higher vulnerability to ischemic conditions and a more sensitive response to teriflunomide compared with cerebellar slice cultures.Our study suggests that teriflunomide,applied as a post-treatment after an oxygenglucose-deprivation,has a protective effect on hippocampal and cerebellar cells in organotypic slice cultures of rats.All procedures were conducted under established standards of the German federal state of North Rhine Westphalia,in accordance with the European Communities Council Directive 2010/63/EU on the protection of animals used for scientific purposes.
基金supported by German Academic Exchange Service to HC。
文摘The nervous system is a highly complex organization composed of its basicunit,the neuronal cells,and specialized supporting cells,the glial cells.The main glial cells in the central nervous system(CNS)are astrocytes,microglia and oligodendrocytes.Astrocytes are the most abundant glial cell type in the CNS.
