Objective\ In order to study the effects of pyrethroids on glutamate (Glu) and gamma aminobutyric acid (GABA) in rat central nervous system. Methods\ Male SD rats were treated with permethrin (7 mg/kg, i.p) or cyperme...Objective\ In order to study the effects of pyrethroids on glutamate (Glu) and gamma aminobutyric acid (GABA) in rat central nervous system. Methods\ Male SD rats were treated with permethrin (7 mg/kg, i.p) or cypermethrin (70 mg/kg, i.p) once a day for 3 days. Glu and GABA immunoreactive cells and transmitters in CNS were studied by immunohistochemical method. Results\ The total number, percentage of positive area and integral optical density of glutamate immunoreactive cell in cerebral cortex, hippocampus decreased significantly in permethrin or cypermethrin, while GABA was enhanced. Cypermethrin is more tent than permethrin on either Glu or GABA. Conclusion\ Disturbance of Glu and GABA is likely to play a role in the development of pyrethroids excitatory neurotoxicity.展开更多
Background:The aim of this study is to assess the effect of baicalein on chronic stress-mediated ovarian dysfunction in a mouse model.Methods:Forty female C57BL/6 mice were randomly divided into four groups as follows...Background:The aim of this study is to assess the effect of baicalein on chronic stress-mediated ovarian dysfunction in a mouse model.Methods:Forty female C57BL/6 mice were randomly divided into four groups as follows:the normal saline group(control,n=10),the daily stress group(daily stress,n=10),the baicalein group(baicalein,n=10),and the daily stress+baicalein group(daily stress+baicalein,n=10).For the daily stress model,we used a restricted stress model.Baicalein(10 mg/kg)was administered by gavage every day,and control mice received normal saline equivalently.Biopsy specimens were harvested after 4 weeks.Measurement of norepinephrine(NE)in serum was performed to assess the psychological stress level of the mice.In addition,histological changes of the uterus and ovaries and the levels of anti-Müllerian hormone(AMH)in serum were assessed to evaluate changes in ovarian function.To detect the underlying mechanisms of the amelioration of baicalein in chronic stress-mediated ovarian dysfunction,immunohistochemical methods,and quantitative real-time polymerase chain reaction were applied to determine the expression of gamma-aminobutyric acid(GABA)receptors.Results:Compared with values in the control group,serum NE concentrations were significantly increased(P<0.001),AMH concentrations were markedly decreased(P<0.01),the thickness of the endometrium was clearly reduced,and the percentage of atretic follicles was significantly increased in the daily stress group(P<0.001),indicating that the chronic stress model was successfully established.In contrast,compared with values in the daily stress group,serum NE concentrations were significantly reduced(P<0.001),AMH concentrations were significantly enhanced(P<0.05),the thickness of the endometrium was clearly increased,and the percentage of atretic follicles was significantly reduced(P<0.001)in the daily stress+baicalein group,indicating that baicalein clearly attenuated the ovarian dysfunction mediated by chronic stress.Moreover,the expression of the GABAB2 receptor in the daily stress group was significantly reduced(P<0.01).In contrast,treatment with baicalein resulted in increased expression of the GABAB2 receptor(P<0.01).Conclusions:Treatment with baicalein ameliorates the enhancing effect of chronic stress on ovarian dysfunction,and the mechanism can be attributed,in part,to the increased expression of the GABAB2 receptor.展开更多
Encephalitis associated with antibodies to gamma-aminobutyric-acid B(GABA-B)is a subgroup of autoimmune synaptic encephalitis with typical features of limbic encephalitis and small cell lung cancer(SCLC).We report a c...Encephalitis associated with antibodies to gamma-aminobutyric-acid B(GABA-B)is a subgroup of autoimmune synaptic encephalitis with typical features of limbic encephalitis and small cell lung cancer(SCLC).We report a case of anti-GABA-B receptor encephalitis in a 57-year-old man who presented with seizures,memory loss,and abnormal behavior.He developed partially neurological responses to immunotherapy,but refused comprehensive tumor screening.The symptoms were aggravated again 4 months later.Workup showed antibodies to GABA-B receptors and tumor screening revealed SCLC.It highlights the importance of early screening of underlying tumor and anti-tumor treatment in paraneoplastic cases.展开更多
A potential treatment for retinal diseases is to induce an endogenous Müller glia(MG)-derived regenerative response to replace damaged neurons.In contrast to mammalian MG,zebrafish MG are capable of mediating spo...A potential treatment for retinal diseases is to induce an endogenous Müller glia(MG)-derived regenerative response to replace damaged neurons.In contrast to mammalian MG,zebrafish MG are capable of mediating spontaneous regeneration.We seek to define the mechanisms that enable retina regeneration in zebrafish in order to identify therapeutic targets to induce mammalian retina regeneration.We previously used pharmacological and genetic methods to inhibit gamma aminobutyric acid A(GABAA)receptors in undamaged zebrafish retinas and showed that such inhibition could induce initiation of retina regeneration,as measured by the dedifferentiation of MG and the appearance of MG-derived proliferating progenitor cells.Here,we show that inhibition of a pharmacologically distinct subset of GABAA receptors(GABAA-ρ)can also induce retina regeneration.Dual inhibition of both GABA receptor subtypes led to enhanced retina regeneration.Gene expression analyses indicate that inhibition of GABAA-ρreceptors induces a canonical retinal regenerative response.Our results support a model in which decreased levels of GABA,such as would occur after retinal cell death or damage,induce dedifferentiation of MG and the generation of proliferating progenitor cells during zebrafish retina regeneration.Animal experiments were approved by the Vanderbilt's Institutional Animal Care and Use Committee(Protocol M1800200)on January 29,2019.展开更多
The progress of modern medicine would be impossible without the use of general anesthetics(GAs).Despite advancements in refining anesthesia approaches,the effects of GAs are not fully reversible upon GA withdrawal.Neu...The progress of modern medicine would be impossible without the use of general anesthetics(GAs).Despite advancements in refining anesthesia approaches,the effects of GAs are not fully reversible upon GA withdrawal.Neurocognitive deficiencies attributed to GA exposure may persist in neonates or endure for weeks to years in the elderly.Human studies on the mechanisms of the long-term adverse effects of GAs are needed to improve the safety of general anesthesia but they are hampered not only by ethical limitations specific to human research,but also by a lack of specific biological markers that can be used in human studies to safely and objectively study such effects.The latter can primarily be attributed to an insufficient understanding of the full range of the biological effects induced by GAs and the molecular mechanisms mediating such effects even in rodents,which are far more extensively studied than any other species.Our most recent experimental findings in rodents suggest that GAs may adversely affect many more people than is currently anticipated.Specifically,we have shown that anesthesia with the commonly used GA sevoflurane induces in exposed animals not only neuroendocrine abnormalities(somatic effects),but also epigenetic reprogramming of germ cells(germ cell effects).The latter may pass the neurobehavioral effects of parental sevoflurane exposure to the offspring,who may be affected even at levels of anesthesia that are not harmful to the exposed parents.The large number of patients who require general anesthesia,the even larger number of their future unexposed offspring whose health may be affected,and a growing number of neurodevelopmental disorders of unknown etiology underscore the translational importance of investigating the intergenerational effects of GAs.In this mini review,we discuss emerging experimental findings on neuroendocrine,epigenetic,and intergenerational effects of GAs.展开更多
Gamma-aminobutyric acid(GABA)possibly plays a causative role in mood disorders.This hypothesis originated with studies on the beneficial effect of valproate in mania and as a mood stabilizer.Since valproate is known f...Gamma-aminobutyric acid(GABA)possibly plays a causative role in mood disorders.This hypothesis originated with studies on the beneficial effect of valproate in mania and as a mood stabilizer.Since valproate is known for its action in increasing the level of GABA,it was indirectly suggested that decreasing levels of GABA were responsible for mood alterations.To identify factors causing the decreased levels of GABA,studies have concentrated on the activity of the enzyme L-glutamic acid decarboxylase(GAD),which catalyzes the transformation of glutamate to GABA,as a decreasing function of this enzyme induces lower levels of the neurotransmitter.Moreover,a very limited amount of research investigated the possible role of glutamic acid decarboxylase antibodies(GADA)in determining a decreased enzymatic function of GAD.If these findings are confirmed,it will be possible to improve diagnosis and treatment of mood disorders.In addition,if the presence of GADA is associated with a genetic trait,this would allow and facilitate early diagnoses.展开更多
文摘Objective\ In order to study the effects of pyrethroids on glutamate (Glu) and gamma aminobutyric acid (GABA) in rat central nervous system. Methods\ Male SD rats were treated with permethrin (7 mg/kg, i.p) or cypermethrin (70 mg/kg, i.p) once a day for 3 days. Glu and GABA immunoreactive cells and transmitters in CNS were studied by immunohistochemical method. Results\ The total number, percentage of positive area and integral optical density of glutamate immunoreactive cell in cerebral cortex, hippocampus decreased significantly in permethrin or cypermethrin, while GABA was enhanced. Cypermethrin is more tent than permethrin on either Glu or GABA. Conclusion\ Disturbance of Glu and GABA is likely to play a role in the development of pyrethroids excitatory neurotoxicity.
基金supported by the Shanghai Science&Technology Commission(18140902502)the National Key Research and Development Program of China(2016YFC1303100)+2 种基金the National Natural Science Foundation of China(81472423)the Shanghai Clinical and Medical Center of Key Program(2017ZZ01016)the Shanghai Science and Technology Innovation Project of Traditional Chinese Medicine(ZYKC201701020).
文摘Background:The aim of this study is to assess the effect of baicalein on chronic stress-mediated ovarian dysfunction in a mouse model.Methods:Forty female C57BL/6 mice were randomly divided into four groups as follows:the normal saline group(control,n=10),the daily stress group(daily stress,n=10),the baicalein group(baicalein,n=10),and the daily stress+baicalein group(daily stress+baicalein,n=10).For the daily stress model,we used a restricted stress model.Baicalein(10 mg/kg)was administered by gavage every day,and control mice received normal saline equivalently.Biopsy specimens were harvested after 4 weeks.Measurement of norepinephrine(NE)in serum was performed to assess the psychological stress level of the mice.In addition,histological changes of the uterus and ovaries and the levels of anti-Müllerian hormone(AMH)in serum were assessed to evaluate changes in ovarian function.To detect the underlying mechanisms of the amelioration of baicalein in chronic stress-mediated ovarian dysfunction,immunohistochemical methods,and quantitative real-time polymerase chain reaction were applied to determine the expression of gamma-aminobutyric acid(GABA)receptors.Results:Compared with values in the control group,serum NE concentrations were significantly increased(P<0.001),AMH concentrations were markedly decreased(P<0.01),the thickness of the endometrium was clearly reduced,and the percentage of atretic follicles was significantly increased in the daily stress group(P<0.001),indicating that the chronic stress model was successfully established.In contrast,compared with values in the daily stress group,serum NE concentrations were significantly reduced(P<0.001),AMH concentrations were significantly enhanced(P<0.05),the thickness of the endometrium was clearly increased,and the percentage of atretic follicles was significantly reduced(P<0.001)in the daily stress+baicalein group,indicating that baicalein clearly attenuated the ovarian dysfunction mediated by chronic stress.Moreover,the expression of the GABAB2 receptor in the daily stress group was significantly reduced(P<0.01).In contrast,treatment with baicalein resulted in increased expression of the GABAB2 receptor(P<0.01).Conclusions:Treatment with baicalein ameliorates the enhancing effect of chronic stress on ovarian dysfunction,and the mechanism can be attributed,in part,to the increased expression of the GABAB2 receptor.
文摘Encephalitis associated with antibodies to gamma-aminobutyric-acid B(GABA-B)is a subgroup of autoimmune synaptic encephalitis with typical features of limbic encephalitis and small cell lung cancer(SCLC).We report a case of anti-GABA-B receptor encephalitis in a 57-year-old man who presented with seizures,memory loss,and abnormal behavior.He developed partially neurological responses to immunotherapy,but refused comprehensive tumor screening.The symptoms were aggravated again 4 months later.Workup showed antibodies to GABA-B receptors and tumor screening revealed SCLC.It highlights the importance of early screening of underlying tumor and anti-tumor treatment in paraneoplastic cases.
基金grants from the NIH R01EY024354-S1 and UO1 EY027265 to JGPand T32 EY021453additional support from the Stevenson family and Gisela Mosig endowments to Vanderbilt University。
文摘A potential treatment for retinal diseases is to induce an endogenous Müller glia(MG)-derived regenerative response to replace damaged neurons.In contrast to mammalian MG,zebrafish MG are capable of mediating spontaneous regeneration.We seek to define the mechanisms that enable retina regeneration in zebrafish in order to identify therapeutic targets to induce mammalian retina regeneration.We previously used pharmacological and genetic methods to inhibit gamma aminobutyric acid A(GABAA)receptors in undamaged zebrafish retinas and showed that such inhibition could induce initiation of retina regeneration,as measured by the dedifferentiation of MG and the appearance of MG-derived proliferating progenitor cells.Here,we show that inhibition of a pharmacologically distinct subset of GABAA receptors(GABAA-ρ)can also induce retina regeneration.Dual inhibition of both GABA receptor subtypes led to enhanced retina regeneration.Gene expression analyses indicate that inhibition of GABAA-ρreceptors induces a canonical retinal regenerative response.Our results support a model in which decreased levels of GABA,such as would occur after retinal cell death or damage,induce dedifferentiation of MG and the generation of proliferating progenitor cells during zebrafish retina regeneration.Animal experiments were approved by the Vanderbilt's Institutional Animal Care and Use Committee(Protocol M1800200)on January 29,2019.
基金Supported by National Institutes of Health,No.R01NS091542National Natural Science Foundation of China,No.81771149,No.U1704165。
文摘The progress of modern medicine would be impossible without the use of general anesthetics(GAs).Despite advancements in refining anesthesia approaches,the effects of GAs are not fully reversible upon GA withdrawal.Neurocognitive deficiencies attributed to GA exposure may persist in neonates or endure for weeks to years in the elderly.Human studies on the mechanisms of the long-term adverse effects of GAs are needed to improve the safety of general anesthesia but they are hampered not only by ethical limitations specific to human research,but also by a lack of specific biological markers that can be used in human studies to safely and objectively study such effects.The latter can primarily be attributed to an insufficient understanding of the full range of the biological effects induced by GAs and the molecular mechanisms mediating such effects even in rodents,which are far more extensively studied than any other species.Our most recent experimental findings in rodents suggest that GAs may adversely affect many more people than is currently anticipated.Specifically,we have shown that anesthesia with the commonly used GA sevoflurane induces in exposed animals not only neuroendocrine abnormalities(somatic effects),but also epigenetic reprogramming of germ cells(germ cell effects).The latter may pass the neurobehavioral effects of parental sevoflurane exposure to the offspring,who may be affected even at levels of anesthesia that are not harmful to the exposed parents.The large number of patients who require general anesthesia,the even larger number of their future unexposed offspring whose health may be affected,and a growing number of neurodevelopmental disorders of unknown etiology underscore the translational importance of investigating the intergenerational effects of GAs.In this mini review,we discuss emerging experimental findings on neuroendocrine,epigenetic,and intergenerational effects of GAs.
文摘Gamma-aminobutyric acid(GABA)possibly plays a causative role in mood disorders.This hypothesis originated with studies on the beneficial effect of valproate in mania and as a mood stabilizer.Since valproate is known for its action in increasing the level of GABA,it was indirectly suggested that decreasing levels of GABA were responsible for mood alterations.To identify factors causing the decreased levels of GABA,studies have concentrated on the activity of the enzyme L-glutamic acid decarboxylase(GAD),which catalyzes the transformation of glutamate to GABA,as a decreasing function of this enzyme induces lower levels of the neurotransmitter.Moreover,a very limited amount of research investigated the possible role of glutamic acid decarboxylase antibodies(GADA)in determining a decreased enzymatic function of GAD.If these findings are confirmed,it will be possible to improve diagnosis and treatment of mood disorders.In addition,if the presence of GADA is associated with a genetic trait,this would allow and facilitate early diagnoses.
