BACKGROUND As the third most abundant element,aluminum is widespread in the environment.Previous studies have shown that aluminum has a neurotoxic effect and its exposure can impair neuronal development and cognitive ...BACKGROUND As the third most abundant element,aluminum is widespread in the environment.Previous studies have shown that aluminum has a neurotoxic effect and its exposure can impair neuronal development and cognitive function.AIM To study the effects of aluminum on epigenetic modification in neural stem cells and neurons.METHODS Neural stem cells were isolated from the forebrain of adult mice.Neurons were isolated from the hippocampi tissues of embryonic day 16-18 mice.AlCl3 at 100 and 200μmol/L was applied to stem cells and neurons.RESULTS Aluminum altered the differentiation of adult neural stem cells and caused apoptosis of newborn neurons while having no significant effects on the proliferation of neural stem cells.Aluminum application also significantly inhibited the dendritic development of hippocampal neurons.Mechanistically,aluminum exposure significantly affected the levels of DNA 5-hydroxy methylcytosine,5-methylcytosine,and N6-methyladenine in stem cells and neurons.CONCLUSION Our findings indicate that aluminum may regulate neuronal development by modulating DNA modifications.展开更多
BACKGROUND: Under the normal circumstance, there exist some synapses with inactive functions in central nervous system (CNS), but these functions are activated following nerve injury. At the early stage of brain injur...BACKGROUND: Under the normal circumstance, there exist some synapses with inactive functions in central nervous system (CNS), but these functions are activated following nerve injury. At the early stage of brain injury, the abnormal functions of brain are varied, and they have very strong plasticity and are corrected easily. OBJECTIVE: To observe the changes of neuronal morphology in hippocampal CA1 region and memory function in newborn rats with hypoxic-ischemic encephalopathy(HIE) from ischemia 6 hours to adult. DESIGN: Completely randomized grouping, controlled experiment. SETTING: Taian Health Center for Women and Children; Taishan Medical College. MATERIALS: Altogether 120 seven-day-old Wistar rats, of clean grade, were provided by the Experimental Animal Center, Shandong University of Traditional Chinese Medicine. Synaptophysin (SYN) polyclonal antibody was provided by Maixin Biological Company, Fuzhou. METHODS: This experiment was carried out in the Laboratory of Morphology, Taishan Medical College between October 2000 and December 2003. ① The newborn rats were randomly divided into 2 groups: model group and control group, 60 rats in each group. Five rats were chosen from each group at postoperative 6 hours, 24 hours, 72 hours, 7 days, 2 weeks and 3 weeks separately for immunohistochemical staining. Fifteen newborn rats were chosen from each group at postoperative 4 weeks and 2 months separately for testing memory ability (After test, 5 rats from each group were sacrificed and used for immunohistochemical staining)② The right common carotid artery of newborn rats of model group was ligated under the anesthetized status. After two hours of incubation, the rats were placed for 2 hours in a container filled with nitrogen oxygen atmosphere containing 0.08 volume fraction of oxygen, thus, HIE models were created; As for the newborn rats in the control group, only blood vessels were isolated, and they were not ligated and hypoxia-treated. ③ Thalamencephal tissue sections of newborn rats of two groups were performed DAB developing and haematoxylin slight staining. Cells with normal nucleous in 250 μm-long granular layer which started from hippocampal CA1 region were counted with image analysis system under high-fold optical microscope (×600), and the thickness of granular layer was measured. The absorbance (A) of positive reactant of SYN in immunohistochemically-stained CA1 region was measured. Learning and memory ability were measured with step through test 3 times successively. ④ t test and paired t test were used for comparing intergroup and intragroup difference of measurement data respectively, and Chi-square for comparing the difference of enumeration data. MAIN OUTCOME MEASURES: Comparison of cytological changes in hippocampal CA1 region and memory ability at different postoperative time points between two groups. RESULTS: Totally 120 newborn rats were involved in the result analysis. ① Cell morphological changes in hippocampal CA1 region: In the control group, with aging, perikaryon, nucleus and nucleolus in cortex of parietal lobe were significantly increased, Nissl body was compacted, the amount of neurons was declined, but the A of SYN positive reactant was relatively increased. In the model group, at postoperative each time point, neurons were seriously shrunk and dark-stained, nucleus was contracted, chromatin was condensed, nucleolus was unclear, even cells disappeared, especially the cells in 6 hours and 24 hours groups. The amount of neurons with normal morphology in hippocampal CA1 region and granular layer thickness in the model group at postoperative each time point were significantly less or smaller than those in the control group at postoperative 6 hours respectively (t =3.002-1.254, P < 0.01). The A value of SYN positive reactant at postoperative 2, 3 and 4 weeks was significantly higher than that at previous time point (t =2.011-2.716,P < 0.05-0.01). ② Test results of learning and memory ability: In the first test, there was no significant difference in the ratio of rats which kept memory ability between two groups (P > 0.05); In the third test, the ratio of rats which kept memory ability in the model group was significantly lower than that in the control group at postoperative 4 weeks and 2 months[53%(8/15),100%(15/15);60%(9/15),93%(14/15),χ 2=2.863,2.901,P < 0.01]. CONCLUSION: The destroyed hippocampal structure induces the decrease of learning and memory ability of developmental rats. Early interference can increase the quality of neurons and also promote functional development of the nervous system.展开更多
Basic helix-loop-helix(bH LH)transcription factors regulate the differentiation of various tissues in a vast diversity of species.The b HLH protein Atonal was first identified as a proneural gene involved in the forma...Basic helix-loop-helix(bH LH)transcription factors regulate the differentiation of various tissues in a vast diversity of species.The b HLH protein Atonal was first identified as a proneural gene involved in the formation of mechanosensory cells and photoreceptor cells in Drosophila(Jarman et al.,1993,1994).Atonal is expressed in sensory organ precursors and is展开更多
The human brain contains an estimated 100 billion neurons that must be systematically organized into functional neural circuits for it to function properly.These circuits range from short-range local signaling network...The human brain contains an estimated 100 billion neurons that must be systematically organized into functional neural circuits for it to function properly.These circuits range from short-range local signaling networks between neighboring neurons to long-range networks formed between various brain regions.Compelling converging evidence indicates that alterations in neural circuits arising from abnormalities during early neuronal development or neurodegeneration contribute significantly to the etiology of neurological disorders.Supporting this notion,efforts to identify genetic causes of these disorders have uncovered an over-representation of genes encoding proteins involved in the processes of neuronal differentiation,maturation,synaptogenesis and synaptic function.Fasciculation and elongation protein zeta-1,a Kinesin-1 adapter,has emerged as a key central player involved in many of these processes.Fasciculation and elongation protein zeta-1-dependent transport of synaptic cargoes and mitochondria is essential for neuronal development and synapse establishment.Furthermore,it acts downstream of guidance cue pathways to regulate axo-dendritic development.Significantly,perturbing its function causes abnormalities in neuronal development and synapse formation both in the brain as well as the peripheral nervous system.Mutations and deletions of the fasciculation and elongation protein zeta-1 gene are linked to neurodevelopmental disorders.Moreover,altered phosphorylation of the protein contributes to neurodegenerative disorders.Together,these findings strongly implicate the importance of fasciculation and elongation protein zeta-1 in the establishment of neuronal circuits and its maintenance.展开更多
Abnormal synchronous neuronal activity has been widely detected by brain imaging of autistic patients,but its underlying neural mechanism remains unclear.Compared with wild-type mice,our in vivo two-photon imaging sho...Abnormal synchronous neuronal activity has been widely detected by brain imaging of autistic patients,but its underlying neural mechanism remains unclear.Compared with wild-type mice,our in vivo two-photon imaging showed that transgenic(Tgl)mice over-expressing human autism risk gene MeCP2 exhibited higher neuronal synchrony in the young but lower synchrony in the adult stage.Whole-cell recording of neuronal pairs in brain slices revealed that higher neuronal synchrony in young postnatal Tgl mice was atributed mainly to more prevalent giant slow inward currents(SICs).Both in vivo and slice imaging further demonstrated more dynamic activity and higher synchrony in astrocytes from young Tgl mice.Blocking astrocytic gap junctions markedly decreased the generation of SICs and overall cell synchrony in the Tgl brain.Furthermore,the expression level of Cx43 protein and the coupling efficiency of astrocyte gap junctions remained unchanged in Tgi mice.Thus,astrocytic gap junctions facilitate but do not act as a direct trigger for the abnormal neuronal synchrony in young Tgl mice,revealing the potential role of the astrocyte network in the pathogenesis of MeCP2 duplication syndrome.展开更多
文摘BACKGROUND As the third most abundant element,aluminum is widespread in the environment.Previous studies have shown that aluminum has a neurotoxic effect and its exposure can impair neuronal development and cognitive function.AIM To study the effects of aluminum on epigenetic modification in neural stem cells and neurons.METHODS Neural stem cells were isolated from the forebrain of adult mice.Neurons were isolated from the hippocampi tissues of embryonic day 16-18 mice.AlCl3 at 100 and 200μmol/L was applied to stem cells and neurons.RESULTS Aluminum altered the differentiation of adult neural stem cells and caused apoptosis of newborn neurons while having no significant effects on the proliferation of neural stem cells.Aluminum application also significantly inhibited the dendritic development of hippocampal neurons.Mechanistically,aluminum exposure significantly affected the levels of DNA 5-hydroxy methylcytosine,5-methylcytosine,and N6-methyladenine in stem cells and neurons.CONCLUSION Our findings indicate that aluminum may regulate neuronal development by modulating DNA modifications.
基金the Grant from Family Planning Commission of Shandong Province,No.97-15
文摘BACKGROUND: Under the normal circumstance, there exist some synapses with inactive functions in central nervous system (CNS), but these functions are activated following nerve injury. At the early stage of brain injury, the abnormal functions of brain are varied, and they have very strong plasticity and are corrected easily. OBJECTIVE: To observe the changes of neuronal morphology in hippocampal CA1 region and memory function in newborn rats with hypoxic-ischemic encephalopathy(HIE) from ischemia 6 hours to adult. DESIGN: Completely randomized grouping, controlled experiment. SETTING: Taian Health Center for Women and Children; Taishan Medical College. MATERIALS: Altogether 120 seven-day-old Wistar rats, of clean grade, were provided by the Experimental Animal Center, Shandong University of Traditional Chinese Medicine. Synaptophysin (SYN) polyclonal antibody was provided by Maixin Biological Company, Fuzhou. METHODS: This experiment was carried out in the Laboratory of Morphology, Taishan Medical College between October 2000 and December 2003. ① The newborn rats were randomly divided into 2 groups: model group and control group, 60 rats in each group. Five rats were chosen from each group at postoperative 6 hours, 24 hours, 72 hours, 7 days, 2 weeks and 3 weeks separately for immunohistochemical staining. Fifteen newborn rats were chosen from each group at postoperative 4 weeks and 2 months separately for testing memory ability (After test, 5 rats from each group were sacrificed and used for immunohistochemical staining)② The right common carotid artery of newborn rats of model group was ligated under the anesthetized status. After two hours of incubation, the rats were placed for 2 hours in a container filled with nitrogen oxygen atmosphere containing 0.08 volume fraction of oxygen, thus, HIE models were created; As for the newborn rats in the control group, only blood vessels were isolated, and they were not ligated and hypoxia-treated. ③ Thalamencephal tissue sections of newborn rats of two groups were performed DAB developing and haematoxylin slight staining. Cells with normal nucleous in 250 μm-long granular layer which started from hippocampal CA1 region were counted with image analysis system under high-fold optical microscope (×600), and the thickness of granular layer was measured. The absorbance (A) of positive reactant of SYN in immunohistochemically-stained CA1 region was measured. Learning and memory ability were measured with step through test 3 times successively. ④ t test and paired t test were used for comparing intergroup and intragroup difference of measurement data respectively, and Chi-square for comparing the difference of enumeration data. MAIN OUTCOME MEASURES: Comparison of cytological changes in hippocampal CA1 region and memory ability at different postoperative time points between two groups. RESULTS: Totally 120 newborn rats were involved in the result analysis. ① Cell morphological changes in hippocampal CA1 region: In the control group, with aging, perikaryon, nucleus and nucleolus in cortex of parietal lobe were significantly increased, Nissl body was compacted, the amount of neurons was declined, but the A of SYN positive reactant was relatively increased. In the model group, at postoperative each time point, neurons were seriously shrunk and dark-stained, nucleus was contracted, chromatin was condensed, nucleolus was unclear, even cells disappeared, especially the cells in 6 hours and 24 hours groups. The amount of neurons with normal morphology in hippocampal CA1 region and granular layer thickness in the model group at postoperative each time point were significantly less or smaller than those in the control group at postoperative 6 hours respectively (t =3.002-1.254, P < 0.01). The A value of SYN positive reactant at postoperative 2, 3 and 4 weeks was significantly higher than that at previous time point (t =2.011-2.716,P < 0.05-0.01). ② Test results of learning and memory ability: In the first test, there was no significant difference in the ratio of rats which kept memory ability between two groups (P > 0.05); In the third test, the ratio of rats which kept memory ability in the model group was significantly lower than that in the control group at postoperative 4 weeks and 2 months[53%(8/15),100%(15/15);60%(9/15),93%(14/15),χ 2=2.863,2.901,P < 0.01]. CONCLUSION: The destroyed hippocampal structure induces the decrease of learning and memory ability of developmental rats. Early interference can increase the quality of neurons and also promote functional development of the nervous system.
基金supported by grants from the Ministry of Education,Culture,Sports,Science and Technology in Japan and Naito Foundation to TCthe Japan Society for the Promotion of Science to MO and TC
文摘Basic helix-loop-helix(bH LH)transcription factors regulate the differentiation of various tissues in a vast diversity of species.The b HLH protein Atonal was first identified as a proneural gene involved in the formation of mechanosensory cells and photoreceptor cells in Drosophila(Jarman et al.,1993,1994).Atonal is expressed in sensory organ precursors and is
基金the Singapore Ministry of Education(T1-2015 Apr-03)the National University of SingaporeInstitute for Health Innovation and Technology to JJEC.
文摘The human brain contains an estimated 100 billion neurons that must be systematically organized into functional neural circuits for it to function properly.These circuits range from short-range local signaling networks between neighboring neurons to long-range networks formed between various brain regions.Compelling converging evidence indicates that alterations in neural circuits arising from abnormalities during early neuronal development or neurodegeneration contribute significantly to the etiology of neurological disorders.Supporting this notion,efforts to identify genetic causes of these disorders have uncovered an over-representation of genes encoding proteins involved in the processes of neuronal differentiation,maturation,synaptogenesis and synaptic function.Fasciculation and elongation protein zeta-1,a Kinesin-1 adapter,has emerged as a key central player involved in many of these processes.Fasciculation and elongation protein zeta-1-dependent transport of synaptic cargoes and mitochondria is essential for neuronal development and synapse establishment.Furthermore,it acts downstream of guidance cue pathways to regulate axo-dendritic development.Significantly,perturbing its function causes abnormalities in neuronal development and synapse formation both in the brain as well as the peripheral nervous system.Mutations and deletions of the fasciculation and elongation protein zeta-1 gene are linked to neurodevelopmental disorders.Moreover,altered phosphorylation of the protein contributes to neurodegenerative disorders.Together,these findings strongly implicate the importance of fasciculation and elongation protein zeta-1 in the establishment of neuronal circuits and its maintenance.
基金supported by the Strategic Priority Research Program of the Chinese Academy of Sciences(XDB32010100)a National Natural Science Foundation of China project(31671113)+1 种基金a Shanghai Municipal Science and Technology Major Project(2018SHZDZX05)and the State Key Laboratory of Neuroscience.
文摘Abnormal synchronous neuronal activity has been widely detected by brain imaging of autistic patients,but its underlying neural mechanism remains unclear.Compared with wild-type mice,our in vivo two-photon imaging showed that transgenic(Tgl)mice over-expressing human autism risk gene MeCP2 exhibited higher neuronal synchrony in the young but lower synchrony in the adult stage.Whole-cell recording of neuronal pairs in brain slices revealed that higher neuronal synchrony in young postnatal Tgl mice was atributed mainly to more prevalent giant slow inward currents(SICs).Both in vivo and slice imaging further demonstrated more dynamic activity and higher synchrony in astrocytes from young Tgl mice.Blocking astrocytic gap junctions markedly decreased the generation of SICs and overall cell synchrony in the Tgl brain.Furthermore,the expression level of Cx43 protein and the coupling efficiency of astrocyte gap junctions remained unchanged in Tgi mice.Thus,astrocytic gap junctions facilitate but do not act as a direct trigger for the abnormal neuronal synchrony in young Tgl mice,revealing the potential role of the astrocyte network in the pathogenesis of MeCP2 duplication syndrome.
