Pediatric autoimmune neuropsychiatric disorders associated with group A streptococcal infections (PANDAS) is a concept that is used to characterize a subset of children with neuropsychiatric symptoms, tic disorders, o...Pediatric autoimmune neuropsychiatric disorders associated with group A streptococcal infections (PANDAS) is a concept that is used to characterize a subset of children with neuropsychiatric symptoms, tic disorders, or obsessive-compulsive disorder (OCD), whose symptoms are exacerbated by group A streptococcal (GAS) infection. PANDAS has been known to cause a sudden onset of reward deficiency syndrome (RDS). RDS includes multiple disorders that are characterized by dopaminergic signaling dysfunction in the brain reward cascade (BRC), which may result in addiction, depression, avoidant behaviors, anxiety, tic disorders, and/or OCD. According to research by Blum et al., the dopamine receptor D2 (DRD2) gene polymorphisms are important prevalent genetic determinants of RDS. The literature demonstrates that infections like Borrelia and Lyme, as well as other infections like group A beta-hemolytic streptococcal (GABHS), can cause an autoimmune reaction and associated antibodies target dopaminergic loci in the mesolimbic region of the brain, which interferes with brain function and potentially causes RDS-like symptoms/behaviors. The treatment of PANDAS remains controversial, especially since there have been limited efficacy studies to date. We propose an innovative potential treatment for PANDAS based on previous clinical trials using a pro-dopamine regulator known as KB220 variants. Our ongoing research suggests that achieving “dopamine homeostasis” by precision-guided DNA testing and pro-dopamine modulation could result in improved therapeutic outcomes.展开更多
Homeostasis of dopamine,a classical neurotransmitter,is a key indicator of neuronal health.Dysfunction in the regulation of dopamine is implicated in a long list of neurological disorders,including addiction,depressio...Homeostasis of dopamine,a classical neurotransmitter,is a key indicator of neuronal health.Dysfunction in the regulation of dopamine is implicated in a long list of neurological disorders,including addiction,depression,and neurodegeneration.The existing methods used to evaluate dopamine homeostasis in vitro are inconvenient and do not allow for continuous non-destructive measurement.In response to this challenge,we introduce an integrated microfluidic system that combines dopaminergic cell culture and differentiation with electroanalytical measurements of extracellular dopamine in real-time at any point during an assay.We used the system to examine the behavior of differentiated SH-SY5Y cells upon exposure to four dopamine transporter ant/agonists(cocaine,ketamine,epigallocatechin gallate,and amphetamine)and study their pharmacokinetics.The IC_(50)values of cocaine,ketamine,and epigallocatechin gallate were determined to be(average±standard deviation)3.7±1.1μM,51.4±17.9μM,and 2.6±0.8μM,respectively.Furthermore,we used the new system to study amphetamine-mediated dopamine release to probe the related phenomena of dopamine transporter-mediated reverse-transport and dopamine release from vesicles.We propose that this platform,which is the first platform to simultaneously evaluate uptake and release,could be useful to screen for drugs and other agents that target dopaminergic neurons and the function of the dopamine transporter.More broadly,this platform should be adaptable for any application that could benefit from high-temporal resolution electroanalysis combined with multi-day cell culture using small numbers of cells.展开更多
We have reported that the central mechanism of acupuncture-induced PRL secretion in non-lactating rats are related to antagonizing hypothalamic dopamine activity; noradrenaline system played little significant role in...We have reported that the central mechanism of acupuncture-induced PRL secretion in non-lactating rats are related to antagonizing hypothalamic dopamine activity; noradrenaline system played little significant role in the acupuncture effect; Υ-aminobutyric-acid system perhaps participated in this effect.This paper further provided evidence that central serotonin and EOP play a stimulatory role in the acupuncture induced secretion of prolactin; acupuncture may antagonize inhibitory effect of H<sub>2</sub> histamine receptor activation on prolactin secretion; the possible role of H<sub>1</sub>-receptor needs further investigation.展开更多
Impaired iron homeostasis may cause damage to dopaminergic neurons and is critically involved in the pathogenesis of Parkinson’s disease. At present, very little is understood about the effect of neonatal iron intake...Impaired iron homeostasis may cause damage to dopaminergic neurons and is critically involved in the pathogenesis of Parkinson’s disease. At present, very little is understood about the effect of neonatal iron intake on behavior in aging animals. Therefore, we hypothesized that increased neonatal iron intake would result in signiifcant behavior abnormalities and striatal dopamine depletion during aging, and Sirtuin 2 contributes to the age-related neurotoxicity. In the present study, we observed that neonatal iron intake （120 μg/g per day） during postnatal days 10–17 resulted in significant behavior abnormalities and striatal dopamine depletion in aging rats. Furthermore, after AK-7 （a selective Sirtuin 2 inhibitor） was injected into the substantia nigra at postnatal 540 days and 570 days （5 μg/side per day）, striatal dopamine depletion was signiifcant-ly diminished and behavior abnormality was improved in aging rats with neonatal iron intake. Experimental ifndings suggest that increased neonatal iron intake may result in Parkinson’s dis-ease-like neurochemical and behavioral deifcits with aging, and inhibition of Sirtuin 2 expression may be a neuroprotective measure in Parkinson’s disease.展开更多
文摘Pediatric autoimmune neuropsychiatric disorders associated with group A streptococcal infections (PANDAS) is a concept that is used to characterize a subset of children with neuropsychiatric symptoms, tic disorders, or obsessive-compulsive disorder (OCD), whose symptoms are exacerbated by group A streptococcal (GAS) infection. PANDAS has been known to cause a sudden onset of reward deficiency syndrome (RDS). RDS includes multiple disorders that are characterized by dopaminergic signaling dysfunction in the brain reward cascade (BRC), which may result in addiction, depression, avoidant behaviors, anxiety, tic disorders, and/or OCD. According to research by Blum et al., the dopamine receptor D2 (DRD2) gene polymorphisms are important prevalent genetic determinants of RDS. The literature demonstrates that infections like Borrelia and Lyme, as well as other infections like group A beta-hemolytic streptococcal (GABHS), can cause an autoimmune reaction and associated antibodies target dopaminergic loci in the mesolimbic region of the brain, which interferes with brain function and potentially causes RDS-like symptoms/behaviors. The treatment of PANDAS remains controversial, especially since there have been limited efficacy studies to date. We propose an innovative potential treatment for PANDAS based on previous clinical trials using a pro-dopamine regulator known as KB220 variants. Our ongoing research suggests that achieving “dopamine homeostasis” by precision-guided DNA testing and pro-dopamine modulation could result in improved therapeutic outcomes.
基金which is supported by the Canada First Research Excellence Fund(CFREF)for funding。
文摘Homeostasis of dopamine,a classical neurotransmitter,is a key indicator of neuronal health.Dysfunction in the regulation of dopamine is implicated in a long list of neurological disorders,including addiction,depression,and neurodegeneration.The existing methods used to evaluate dopamine homeostasis in vitro are inconvenient and do not allow for continuous non-destructive measurement.In response to this challenge,we introduce an integrated microfluidic system that combines dopaminergic cell culture and differentiation with electroanalytical measurements of extracellular dopamine in real-time at any point during an assay.We used the system to examine the behavior of differentiated SH-SY5Y cells upon exposure to four dopamine transporter ant/agonists(cocaine,ketamine,epigallocatechin gallate,and amphetamine)and study their pharmacokinetics.The IC_(50)values of cocaine,ketamine,and epigallocatechin gallate were determined to be(average±standard deviation)3.7±1.1μM,51.4±17.9μM,and 2.6±0.8μM,respectively.Furthermore,we used the new system to study amphetamine-mediated dopamine release to probe the related phenomena of dopamine transporter-mediated reverse-transport and dopamine release from vesicles.We propose that this platform,which is the first platform to simultaneously evaluate uptake and release,could be useful to screen for drugs and other agents that target dopaminergic neurons and the function of the dopamine transporter.More broadly,this platform should be adaptable for any application that could benefit from high-temporal resolution electroanalysis combined with multi-day cell culture using small numbers of cells.
基金Project supported by the National Natural Science Fund
文摘We have reported that the central mechanism of acupuncture-induced PRL secretion in non-lactating rats are related to antagonizing hypothalamic dopamine activity; noradrenaline system played little significant role in the acupuncture effect; Υ-aminobutyric-acid system perhaps participated in this effect.This paper further provided evidence that central serotonin and EOP play a stimulatory role in the acupuncture induced secretion of prolactin; acupuncture may antagonize inhibitory effect of H<sub>2</sub> histamine receptor activation on prolactin secretion; the possible role of H<sub>1</sub>-receptor needs further investigation.
基金supported by the National Natural Science Foundation of China,No.81171204,81171203,30772280,81200871,and 81200921a grant from the Project of Shanghai Municipal Education Commission of China,No.14YZ046+2 种基金a grant from the Project of Shanghai Municipal Health and Family Planning Commission of China,No.20134049a grant from the Project of Shanghai Jiao Tong University of China,No.YG2013MS22a grant from the Projects of Shanghai Committee of Science and Technology of China,No.11nm0503300 and 12XD1403800
文摘Impaired iron homeostasis may cause damage to dopaminergic neurons and is critically involved in the pathogenesis of Parkinson’s disease. At present, very little is understood about the effect of neonatal iron intake on behavior in aging animals. Therefore, we hypothesized that increased neonatal iron intake would result in signiifcant behavior abnormalities and striatal dopamine depletion during aging, and Sirtuin 2 contributes to the age-related neurotoxicity. In the present study, we observed that neonatal iron intake （120 μg/g per day） during postnatal days 10–17 resulted in significant behavior abnormalities and striatal dopamine depletion in aging rats. Furthermore, after AK-7 （a selective Sirtuin 2 inhibitor） was injected into the substantia nigra at postnatal 540 days and 570 days （5 μg/side per day）, striatal dopamine depletion was signiifcant-ly diminished and behavior abnormality was improved in aging rats with neonatal iron intake. Experimental ifndings suggest that increased neonatal iron intake may result in Parkinson’s dis-ease-like neurochemical and behavioral deifcits with aging, and inhibition of Sirtuin 2 expression may be a neuroprotective measure in Parkinson’s disease.
