Intracerebroventricular administration (ICV) of streptozotocin (STZ) in rats has been associated to desensitization of the insulin receptor (IR) and biochemical changes similar to those occurring in Alzheimer’s disea...Intracerebroventricular administration (ICV) of streptozotocin (STZ) in rats has been associated to desensitization of the insulin receptor (IR) and biochemical changes similar to those occurring in Alzheimer’s disease (AD) or older brains, so it has been proposed as a suitable model for studying some of the pathological features of AD sporadic type (SAD). In this study, we investigated the role of glycogen synthase kinase 3β (GSK3β) and protein phosphatase 2A (PP2A) in the regulation of the phosphorylation of tau (p-tau). Results showed that ICV-STZ treated rats had deficits in short- (1.5-h) and long-term (24- and 48-h) memory after one month of ICV-STZ treatment and six months relative to control rats. The memory deficit was associated to increasing [F(3, 12) = 31.48, p β (p-GSK3β) and PP2A in hippocampus and PFC, indicating that GSK3β and PP2A contributed to regulation of p-tau. These data supporting the model with ICV-STZ in rat are adequate to study the progressive memory impairment associated to hyperphosphorylation of tau and the cascade of insulin receptor signaling;confirm that phosphatidyl-inositol-3 kinase-protein kinase B (PI3K-PKB/Akt-GSK3β) and PP2A are involved in the modulation of proteins responsible for the regulation of neurodegeneration in AD.展开更多
Our previous study together with other inves- tigations have reported that neonatal hypoxia or ischemia induces long-term cognitive through brain inflammation impairment, at least in part and hypomyelination. How- eve...Our previous study together with other inves- tigations have reported that neonatal hypoxia or ischemia induces long-term cognitive through brain inflammation impairment, at least in part and hypomyelination. How- ever, the detailed mechanisms are not fully understood. Here, we used a rodent model of neonatal hypoxia by subjecting postnatal day 0 （P0） rat pups to systemic hypoxia （3.5 h）. We found that neonatal hypoxia increased the glutamate content and initiated inflammatory responses at 4 h and 1 day after hypoxia, caused hypomyelination in the corpus callosum, and impaired hippocampus-dependent learning and memory when assessed 30-60 days after hypoxia. Interestingly, much of the hypoxia-induced brain damage was ameliorated by treatment with the ATP ana- logue 21,3-0-（2,4,6-trinitrophenyl）-adenosine 5^-triphos- phate （TNP-ATP; blocks all ionotropic P2Xl-7 receptors）, whereas treatment with pyridoxalphosphate-6-azophenyl- 2＇,4＇-disulphonic acid （PPADS; inhibits P2X1-3 and P2X5- 7 receptors） was less neuroprotective. Our data indicated that activation of ionotropic ATP receptors might be par- tially, if not fully, involved in glutamate deregulation, neuroinflammation, hypomyelination, and cognitive dys- function after neonatal hypoxia.展开更多
Attention Deficit Hyperactivity Disorder (ADHD) is a childhood onset autoregulation disorder characterized by attention deficit, hyperactivity and/or impul- siveness, which results in social and academic functional im...Attention Deficit Hyperactivity Disorder (ADHD) is a childhood onset autoregulation disorder characterized by attention deficit, hyperactivity and/or impul- siveness, which results in social and academic functional impairment. ADHD has a complex aetiology: along with genetic factors, anomalies in several cere-bral districts have been reported. We describe the case of a 9 year old boy with glucose-6-phosphate dehydrogenase deficiency in association with memory, behavioural and attentive disabilities. The patient’s clinical history is characterized by cerebral stroke at 3 years of age during a febrile episode, resulted in slight hemiparesis. Neuroimaging revealed a cystic lesion in the anterior portion of the right lenticular nucleus. Neuropsychological and psychiatric assess- ment evidenced alterations of executive functions. Diagnosis of ADHD secondary to lesion of the basal ganglia was made. We report the patient’s clinical profile in the light of current evidence pointing towards dysfunction of the basal ganglia as a crucial aetiological factor in memory and executive function impairment.展开更多
Episodic autobiographical memory(AM) allows one, through the recollection of sensory-perceptual details, thoughts and feelings, to become aware of an event as belonging to one's own past as well as being able to p...Episodic autobiographical memory(AM) allows one, through the recollection of sensory-perceptual details, thoughts and feelings, to become aware of an event as belonging to one's own past as well as being able to project into one's future. Because AM provides a sense of self-continuity, contributes to the integrity of the self, and helps predicting future experiences, any deficit of AM may have debilitating consequences for everyday life functioning. Understanding AM failure and the underlying neural mechanisms has the potential to shed light on brain reorganization mechanisms and engagement of compensatory processes. Functional magnetic resonance imaging(fMRI) provides the most promising imaging method to tackle these issues. We reviewed evidence from the few studies that used fMRI to investigate the functionality of the residual tissue, the neural reorganization and compensatory mechanisms in patients with neurological conditions due to impaired medial temporal lobe. Overall, these studies highlight the importance of the left hippocampus, which when atrophied and not functional leads to AM deficits but its residual functionality may support relatively normal AM recollection. When damaged hippocampal tissue is not functional, other brain regions(e.g., the medial prefrontal cortex) may be involved to compensate impairment, but they appear generally ineffective to support detailed episodic recollection.展开更多
There is accumulating clinical evidence that chemotherapeutic agents induce neurological side effects, including memory deficits and mood disorders, in cancer patients who have undergone chemotherapeutic treatments. T...There is accumulating clinical evidence that chemotherapeutic agents induce neurological side effects, including memory deficits and mood disorders, in cancer patients who have undergone chemotherapeutic treatments. This review focuses on chemotherapy-induced neurodegeneration and hippocampal dysfunctions and related mechanisms as measured by in vivo and in vitro approaches. These investigations are helpful in determining how best to further explore the causa mechanisms of chemotherapy-induced neurological side effects and in providing direction for the future development of novel optimized chemotherapeutic agents.展开更多
Background Human amniotic epithelial cells （HAECs）, which have characteristics of both embryonic and pluripotent stem cells, are therefore a candidate in cell therapy without creating legal or ethical problems. In t...Background Human amniotic epithelial cells （HAECs）, which have characteristics of both embryonic and pluripotent stem cells, are therefore a candidate in cell therapy without creating legal or ethical problems. In the present study, we aimed to investigate the effects of intracerebroventricular transplantation of HAECs on doubly transgenic mice of Alzheimer＇s disease （AD） coexpressing presenilin-1 （PS1） and mutant Sweden amyloid precursor protein （APPswe） genes. Methods The offspring mice genotypes were detected using PCR identification of APPswe and PS1 gene. The doubly transgenic （TG） mice （n=20） and wild-type （WT） mice （n=20） were randomly divided into two groups respectively： the transplantation group treated with HAECs and the control group with phosphate buffered saline. Six radial arm water maze test was used to assess the spatial memory in the TG and WT mice. Amyloid plaques and neurofibrillary tangles were analyzed using congo red and acid-silver methenamine staining respectively. was used to track the survival of HAECs. Immunohistochemistry was used octamer-binding protein 4 （Oct-4） and Nanog in the HAECs. High performance measure acetylcholine in hippocampus. The density of cholinergic neurons in hippocampus was measured using acetylcholinesterase staining. Immunofluorescence cytochemistry to determine the expression of quid chromatography was used to basal forebrain and nerve fibers in Results Amyloid deposition occurred in hippocampus and frontal cortex in the double TG mice aged 8 months, but not in WT mice. The results also showed that transplanted HAECs can survive for at least 8 weeks and migrate to the third ventricle without immune rejection. The graft HAECs can also express the specific marker Oct-4 and Nanog of stem cell. Compared with the control group, transplantation of HAECs can not only significantly improve the spatial memory of the TG mice, but also increase acetylcholine concentration and the number of hippocampal cholinergic neurites. Conclusi展开更多
文摘Intracerebroventricular administration (ICV) of streptozotocin (STZ) in rats has been associated to desensitization of the insulin receptor (IR) and biochemical changes similar to those occurring in Alzheimer’s disease (AD) or older brains, so it has been proposed as a suitable model for studying some of the pathological features of AD sporadic type (SAD). In this study, we investigated the role of glycogen synthase kinase 3β (GSK3β) and protein phosphatase 2A (PP2A) in the regulation of the phosphorylation of tau (p-tau). Results showed that ICV-STZ treated rats had deficits in short- (1.5-h) and long-term (24- and 48-h) memory after one month of ICV-STZ treatment and six months relative to control rats. The memory deficit was associated to increasing [F(3, 12) = 31.48, p β (p-GSK3β) and PP2A in hippocampus and PFC, indicating that GSK3β and PP2A contributed to regulation of p-tau. These data supporting the model with ICV-STZ in rat are adequate to study the progressive memory impairment associated to hyperphosphorylation of tau and the cascade of insulin receptor signaling;confirm that phosphatidyl-inositol-3 kinase-protein kinase B (PI3K-PKB/Akt-GSK3β) and PP2A are involved in the modulation of proteins responsible for the regulation of neurodegeneration in AD.
基金supported by grants from the National Natural Science Foundation of China(81200939 and31260242)National Science and Technology Supporting Plan of China(2014BAI01B00)+3 种基金Natural Science Foundation of Yunnan Province,China(2011FB060)the National Undergraduate Innovation Fund of China(201310678001)the Undergraduate Innovation Fund of Yunnan Province,China(6011202105)Department of Pathology and Pathophysiology, School of Basic Medical Science, Kunming Medical University for his support throughout the study
文摘Our previous study together with other inves- tigations have reported that neonatal hypoxia or ischemia induces long-term cognitive through brain inflammation impairment, at least in part and hypomyelination. How- ever, the detailed mechanisms are not fully understood. Here, we used a rodent model of neonatal hypoxia by subjecting postnatal day 0 （P0） rat pups to systemic hypoxia （3.5 h）. We found that neonatal hypoxia increased the glutamate content and initiated inflammatory responses at 4 h and 1 day after hypoxia, caused hypomyelination in the corpus callosum, and impaired hippocampus-dependent learning and memory when assessed 30-60 days after hypoxia. Interestingly, much of the hypoxia-induced brain damage was ameliorated by treatment with the ATP ana- logue 21,3-0-（2,4,6-trinitrophenyl）-adenosine 5^-triphos- phate （TNP-ATP; blocks all ionotropic P2Xl-7 receptors）, whereas treatment with pyridoxalphosphate-6-azophenyl- 2＇,4＇-disulphonic acid （PPADS; inhibits P2X1-3 and P2X5- 7 receptors） was less neuroprotective. Our data indicated that activation of ionotropic ATP receptors might be par- tially, if not fully, involved in glutamate deregulation, neuroinflammation, hypomyelination, and cognitive dys- function after neonatal hypoxia.
文摘Attention Deficit Hyperactivity Disorder (ADHD) is a childhood onset autoregulation disorder characterized by attention deficit, hyperactivity and/or impul- siveness, which results in social and academic functional impairment. ADHD has a complex aetiology: along with genetic factors, anomalies in several cere-bral districts have been reported. We describe the case of a 9 year old boy with glucose-6-phosphate dehydrogenase deficiency in association with memory, behavioural and attentive disabilities. The patient’s clinical history is characterized by cerebral stroke at 3 years of age during a febrile episode, resulted in slight hemiparesis. Neuroimaging revealed a cystic lesion in the anterior portion of the right lenticular nucleus. Neuropsychological and psychiatric assess- ment evidenced alterations of executive functions. Diagnosis of ADHD secondary to lesion of the basal ganglia was made. We report the patient’s clinical profile in the light of current evidence pointing towards dysfunction of the basal ganglia as a crucial aetiological factor in memory and executive function impairment.
文摘Episodic autobiographical memory(AM) allows one, through the recollection of sensory-perceptual details, thoughts and feelings, to become aware of an event as belonging to one's own past as well as being able to project into one's future. Because AM provides a sense of self-continuity, contributes to the integrity of the self, and helps predicting future experiences, any deficit of AM may have debilitating consequences for everyday life functioning. Understanding AM failure and the underlying neural mechanisms has the potential to shed light on brain reorganization mechanisms and engagement of compensatory processes. Functional magnetic resonance imaging(fMRI) provides the most promising imaging method to tackle these issues. We reviewed evidence from the few studies that used fMRI to investigate the functionality of the residual tissue, the neural reorganization and compensatory mechanisms in patients with neurological conditions due to impaired medial temporal lobe. Overall, these studies highlight the importance of the left hippocampus, which when atrophied and not functional leads to AM deficits but its residual functionality may support relatively normal AM recollection. When damaged hippocampal tissue is not functional, other brain regions(e.g., the medial prefrontal cortex) may be involved to compensate impairment, but they appear generally ineffective to support detailed episodic recollection.
基金supported by a National Research Foundation of Korea Grant funded by the Korean Government, No. NRF-2011-0003380 2012R1A1B44001262a grant from Animal Medical Institute of Chonnam National University
文摘There is accumulating clinical evidence that chemotherapeutic agents induce neurological side effects, including memory deficits and mood disorders, in cancer patients who have undergone chemotherapeutic treatments. This review focuses on chemotherapy-induced neurodegeneration and hippocampal dysfunctions and related mechanisms as measured by in vivo and in vitro approaches. These investigations are helpful in determining how best to further explore the causa mechanisms of chemotherapy-induced neurological side effects and in providing direction for the future development of novel optimized chemotherapeutic agents.
基金The project was supported by grants from the National Natural Science Foundation of China （No. 30271325） and the Major State Basic Resarch Development Program of China （＂973＂ Program） （No. 2005CB522604）.
文摘Background Human amniotic epithelial cells （HAECs）, which have characteristics of both embryonic and pluripotent stem cells, are therefore a candidate in cell therapy without creating legal or ethical problems. In the present study, we aimed to investigate the effects of intracerebroventricular transplantation of HAECs on doubly transgenic mice of Alzheimer＇s disease （AD） coexpressing presenilin-1 （PS1） and mutant Sweden amyloid precursor protein （APPswe） genes. Methods The offspring mice genotypes were detected using PCR identification of APPswe and PS1 gene. The doubly transgenic （TG） mice （n=20） and wild-type （WT） mice （n=20） were randomly divided into two groups respectively： the transplantation group treated with HAECs and the control group with phosphate buffered saline. Six radial arm water maze test was used to assess the spatial memory in the TG and WT mice. Amyloid plaques and neurofibrillary tangles were analyzed using congo red and acid-silver methenamine staining respectively. was used to track the survival of HAECs. Immunohistochemistry was used octamer-binding protein 4 （Oct-4） and Nanog in the HAECs. High performance measure acetylcholine in hippocampus. The density of cholinergic neurons in hippocampus was measured using acetylcholinesterase staining. Immunofluorescence cytochemistry to determine the expression of quid chromatography was used to basal forebrain and nerve fibers in Results Amyloid deposition occurred in hippocampus and frontal cortex in the double TG mice aged 8 months, but not in WT mice. The results also showed that transplanted HAECs can survive for at least 8 weeks and migrate to the third ventricle without immune rejection. The graft HAECs can also express the specific marker Oct-4 and Nanog of stem cell. Compared with the control group, transplantation of HAECs can not only significantly improve the spatial memory of the TG mice, but also increase acetylcholine concentration and the number of hippocampal cholinergic neurites. Conclusi
