Amyotrophic lateral sclerosis（ALS） and motor neuron diseases（MNDs） are progressive neurodegenerative diseases that affect nerve cells in the brain affecting upper and lower motor neurons（UMNs/LMNs）, brain stem a...Amyotrophic lateral sclerosis（ALS） and motor neuron diseases（MNDs） are progressive neurodegenerative diseases that affect nerve cells in the brain affecting upper and lower motor neurons（UMNs/LMNs）, brain stem and spinal cord. The clinical phenotype is characterized by loss of motor neurons（MNs）, muscular weakness and atrophy eventually leading to paralysis and death due to respiratory failure within 3–5 years after disease onset. No effective treatment or cure is currently available that halts or reverses ALS and MND except FDA approved drug riluzole that only modestly slows the progression of ALS in some patients. Recent advances in human derived induced pluripotent stem cells have made it possible for the first time to obtain substantial amounts of human cells to recapitulate in vitro “disease in dish” and test some of the underlying pathogenetic mechanisms involved in ALS and MNDs. In this review, I discussed the opportunities and challenges of induced pluropotent stem cells-derived motor neurons for treatment of ALS and MND patients with special emphasis on their implications in finding a cure for ALS and MNDs.展开更多
Neurotrophins：Neurotrophins are peptides or proteins that are known to regulate neuronal viability,development,and function Beyond synaptic plasticity,neurotrophins protect neurons from apoptosis and also promote neu...Neurotrophins：Neurotrophins are peptides or proteins that are known to regulate neuronal viability,development,and function Beyond synaptic plasticity,neurotrophins protect neurons from apoptosis and also promote neurogenesis to recover neuronal defici even in adulthood.展开更多
The sense of smell is important for human quality of life. This sophisticated sensorial system relies on the detection of odorant molecules that engage receptors expressed in the cilia of dedicated neurons that consti...The sense of smell is important for human quality of life. This sophisticated sensorial system relies on the detection of odorant molecules that engage receptors expressed in the cilia of dedicated neurons that constitute the olfactory epithelium（OE）. Importantly, the OE is a highly active site of adult neurogenesis where short-lived neurons are efficiently replenished, even after massive neuronal cell loss. It is suggested that the degree of olfactory function recovery after OE injury may depend on the nature of the lesion（traumatic, chemical, infectious or inflammatory）, as well on the velocity of cellular regeneration. Topical steroidal anti-inflammatory drugs, such as glucocorticoids, are routinely prescribed for treating upper airway inflammatory conditions, such as chronic rhinosinusitis. While the therapeutic strategy aims to minimize the inflammatory damage and dysfunction to nasal air conduction, new evidences raise concerns if such drugs may impair neuronal regeneration in the OE. In consequence, new directions are necessary in terms of drug development or prescription, in order to preserve olfactory function through lifelong repeated episodes of chronic inflammation in the upper respiratory tract. Here we discuss mechanisms involved in glucocorticoid deleterious effects to OE regeneration and possible therapeutic alternatives considering relevant side effects.展开更多
AIM: To develop an in vitro model based on neural stem cells derived from transgenic animals, to be used in the study of pathological mechanisms of Alzheimer's disease and for testing new molecules.METHODS: Neural...AIM: To develop an in vitro model based on neural stem cells derived from transgenic animals, to be used in the study of pathological mechanisms of Alzheimer's disease and for testing new molecules.METHODS: Neural stem cells(NSCs) were isolated from the subventricular zone of Wild type(Wt) and Tg2576 mice. Primary and secondary neurosphere generation was studied, analysing population doubling and the cell yield per animal. Secondary neurospheres were dissociated and plated on MCM Gel Cultrex 2D and after 6 d in vitro(DIVs) in mitogen withdrawal conditions,spontaneous differentiation was studied using specific neural markers(MAP2 and TuJ-1 for neurons, GFAP forastroglial cells and CNPase for oligodendrocytes). Gene expression pathways were analysed in secondary neurospheres, using the QIAGEN PCR array for neurogenesis, comparing the Tg2576 derived cell expression with the Wt cells. Proteins encoded by the altered genes were clustered using STRING web software.RESULTS: As revealed by 6E10 positive staining, all Tg2576 derived cells retain the expression of the human transgenic Amyloid Precursor Protein. Tg2576 derived primary neurospheres show a decrease in population doubling. Morphological analysis of differentiated NSCs reveals a decrease in MAP2- and an increase in GFAP-positive cells in Tg2576 derived cells. Analysing the branching of TuJ-1 positive cells, a clear decrease in neurite number and length is observed in Tg2576 cells.The gene expression neurogenesis pathway revealed11 altered genes in Tg2576 NSCs compared to Wt.CONCLUSION: Tg2576 NSCs represent an appropriate AD in vitro model resembling some cellular alterations observed in vivo, both as stem and differentiated cells.展开更多
AIM:To investigate whether cocktail theraphy combined with of neuroprotectants may have more advantages over single agents in treating focal cerebral ischemic cascade.METHODS:With the use of suture occlusin techique,t...AIM:To investigate whether cocktail theraphy combined with of neuroprotectants may have more advantages over single agents in treating focal cerebral ischemic cascade.METHODS:With the use of suture occlusin techique,the right middle cerebral artery in rats was occluded.Tirty minutes later,Frutose 1,6 diphosphate(FDP) (50 mg/kg,n=20), MK 801(1 mg/kg,n=20) and N acetylcystein (NAC)(150 mg/kg,n=20) were singly or combinantly infused intraperitoneally.At the same time the cocktail treated group(n=20)were infused the above agents combinationly and the control group(n=20)were infused normal saline intraperitoneally.6 hours and 24 hours after focal cerebral ischemia the animals were weighted and neurologically assessed on 5 point scale.The animals were killed,brains were stained 2,3,5 triphenyltetrazolium chloride for assessment of the infarct volume and then embedden onto slides with paraffin for morphological assessment and terminal transferase dUTP nick ending labeling(TUNEL )were carried out for apoptosis and immunohistochemistry were carried out to investigate the changes in bcl 2.RESULTS:All Neuroprotectants decreased volume of infarction (P< 0.05,F test).While cocktail treated group showed more distinct decrease than other groups(P< 0.05,F test).FDP treated group did not decrease the apoptosis of the neurons and did not increase the bcl 2 expression as well.MK 801 treated group,NAC treated group and cocktail treated group significantly decreased the apoptosis of the neurons and increased the bcl 2 expression (P< 0.05,F test).With cocktail treated group showing more distinct effect (P< 0.05,F test).CONCLUSION:Cocktail may be more effective than single neuroprotectant in this modle.展开更多
Radix Salviae Miltiorrhizae (RSM), a well-known traditional Chinese medicinal herb, has been used to improve blood circulation and resolve blood stasis. We have previously found that RSM has neuroprotective effect on ...Radix Salviae Miltiorrhizae (RSM), a well-known traditional Chinese medicinal herb, has been used to improve blood circulation and resolve blood stasis. We have previously found that RSM has neuroprotective effect on ischemia and/ or ischemia-reperfusion rats. The purpose of this study was to obtain further information on the mechanism of the RSM-in-duced neuroprotection and to examine the neuroprotective effect on neurons exposed to anoxia. The effect of RSM on anoxic damage in cultured hippocampal neurons of neonatal rat was investigated by using morphological changes and heat shock protein 70kD (HSP70) expression as indicators. RSM given 0.5h before 2h-anoxia followed by 48 hours reoxygenation could significantly increase survival rate of hippocampal neurons and number of HSP70 positive cells. The results suggest that RSM has a direct neuroprotective effects on anoxic damage in hippocampal neurons.展开更多
To explore the possibility of hydrogen sulfide (H 2S) as a messenger molecule in cardiovascular system, the authors discovered that H 2S (5×10 -5 -5×10 -4 mol·L -1 )exerted an effect on inhibiting endot...To explore the possibility of hydrogen sulfide (H 2S) as a messenger molecule in cardiovascular system, the authors discovered that H 2S (5×10 -5 -5×10 -4 mol·L -1 )exerted an effect on inhibiting endothelin 1 induced proliferation of cultured vascular smooth muscle cells (VSMCs) of rats in vitro . The 3H TdR incorporation decreased by 16.8%～37.4% in H 2S treated VSMCs as compared with the controls ( P <0.01). The inhibitory effect was found to be associated with reduced activity of MAPK. The authors also observed that endogenous H 2S levels markedly increased in vessels of rats with either endotoxic shock or septic shock [H 2S level (pmol·min -1 ·mg -1 ):tail artery (16.18±2.06) vs (8.12±0.55);mesenteric artery (10.17±1.11) vs (6.19 ±0.55);pulmonary artery(11.38±1.24) vs (5.27±0.51); aorta(6.21±0.48) vs (4.10± 0.28), P < 0.01 ]. The above findings suggested that H 2S might play an important role in the regulation of cardiovascular pathophysiologic events.展开更多
文摘Amyotrophic lateral sclerosis（ALS） and motor neuron diseases（MNDs） are progressive neurodegenerative diseases that affect nerve cells in the brain affecting upper and lower motor neurons（UMNs/LMNs）, brain stem and spinal cord. The clinical phenotype is characterized by loss of motor neurons（MNs）, muscular weakness and atrophy eventually leading to paralysis and death due to respiratory failure within 3–5 years after disease onset. No effective treatment or cure is currently available that halts or reverses ALS and MND except FDA approved drug riluzole that only modestly slows the progression of ALS in some patients. Recent advances in human derived induced pluripotent stem cells have made it possible for the first time to obtain substantial amounts of human cells to recapitulate in vitro “disease in dish” and test some of the underlying pathogenetic mechanisms involved in ALS and MNDs. In this review, I discussed the opportunities and challenges of induced pluropotent stem cells-derived motor neurons for treatment of ALS and MND patients with special emphasis on their implications in finding a cure for ALS and MNDs.
文摘Neurotrophins：Neurotrophins are peptides or proteins that are known to regulate neuronal viability,development,and function Beyond synaptic plasticity,neurotrophins protect neurons from apoptosis and also promote neurogenesis to recover neuronal defici even in adulthood.
基金supported by research grants to IG from Fundacao de Amparo a Pesquisa do Estado de Sao Paulo(FAPESP 2007/53732-8)Conselho Nacional de Desenvolvimento Científico e Tecnológico(CNPq 484869/2012-4)CEPID Redoxoma(FAPESP 2013/07937-8)
文摘The sense of smell is important for human quality of life. This sophisticated sensorial system relies on the detection of odorant molecules that engage receptors expressed in the cilia of dedicated neurons that constitute the olfactory epithelium（OE）. Importantly, the OE is a highly active site of adult neurogenesis where short-lived neurons are efficiently replenished, even after massive neuronal cell loss. It is suggested that the degree of olfactory function recovery after OE injury may depend on the nature of the lesion（traumatic, chemical, infectious or inflammatory）, as well on the velocity of cellular regeneration. Topical steroidal anti-inflammatory drugs, such as glucocorticoids, are routinely prescribed for treating upper airway inflammatory conditions, such as chronic rhinosinusitis. While the therapeutic strategy aims to minimize the inflammatory damage and dysfunction to nasal air conduction, new evidences raise concerns if such drugs may impair neuronal regeneration in the OE. In consequence, new directions are necessary in terms of drug development or prescription, in order to preserve olfactory function through lifelong repeated episodes of chronic inflammation in the upper respiratory tract. Here we discuss mechanisms involved in glucocorticoid deleterious effects to OE regeneration and possible therapeutic alternatives considering relevant side effects.
基金Supported by Regione Emilia Romagna,POR-FESR 2011-2014
文摘AIM: To develop an in vitro model based on neural stem cells derived from transgenic animals, to be used in the study of pathological mechanisms of Alzheimer's disease and for testing new molecules.METHODS: Neural stem cells(NSCs) were isolated from the subventricular zone of Wild type(Wt) and Tg2576 mice. Primary and secondary neurosphere generation was studied, analysing population doubling and the cell yield per animal. Secondary neurospheres were dissociated and plated on MCM Gel Cultrex 2D and after 6 d in vitro(DIVs) in mitogen withdrawal conditions,spontaneous differentiation was studied using specific neural markers(MAP2 and TuJ-1 for neurons, GFAP forastroglial cells and CNPase for oligodendrocytes). Gene expression pathways were analysed in secondary neurospheres, using the QIAGEN PCR array for neurogenesis, comparing the Tg2576 derived cell expression with the Wt cells. Proteins encoded by the altered genes were clustered using STRING web software.RESULTS: As revealed by 6E10 positive staining, all Tg2576 derived cells retain the expression of the human transgenic Amyloid Precursor Protein. Tg2576 derived primary neurospheres show a decrease in population doubling. Morphological analysis of differentiated NSCs reveals a decrease in MAP2- and an increase in GFAP-positive cells in Tg2576 derived cells. Analysing the branching of TuJ-1 positive cells, a clear decrease in neurite number and length is observed in Tg2576 cells.The gene expression neurogenesis pathway revealed11 altered genes in Tg2576 NSCs compared to Wt.CONCLUSION: Tg2576 NSCs represent an appropriate AD in vitro model resembling some cellular alterations observed in vivo, both as stem and differentiated cells.
文摘AIM:To investigate whether cocktail theraphy combined with of neuroprotectants may have more advantages over single agents in treating focal cerebral ischemic cascade.METHODS:With the use of suture occlusin techique,the right middle cerebral artery in rats was occluded.Tirty minutes later,Frutose 1,6 diphosphate(FDP) (50 mg/kg,n=20), MK 801(1 mg/kg,n=20) and N acetylcystein (NAC)(150 mg/kg,n=20) were singly or combinantly infused intraperitoneally.At the same time the cocktail treated group(n=20)were infused the above agents combinationly and the control group(n=20)were infused normal saline intraperitoneally.6 hours and 24 hours after focal cerebral ischemia the animals were weighted and neurologically assessed on 5 point scale.The animals were killed,brains were stained 2,3,5 triphenyltetrazolium chloride for assessment of the infarct volume and then embedden onto slides with paraffin for morphological assessment and terminal transferase dUTP nick ending labeling(TUNEL )were carried out for apoptosis and immunohistochemistry were carried out to investigate the changes in bcl 2.RESULTS:All Neuroprotectants decreased volume of infarction (P< 0.05,F test).While cocktail treated group showed more distinct decrease than other groups(P< 0.05,F test).FDP treated group did not decrease the apoptosis of the neurons and did not increase the bcl 2 expression as well.MK 801 treated group,NAC treated group and cocktail treated group significantly decreased the apoptosis of the neurons and increased the bcl 2 expression (P< 0.05,F test).With cocktail treated group showing more distinct effect (P< 0.05,F test).CONCLUSION:Cocktail may be more effective than single neuroprotectant in this modle.
文摘Radix Salviae Miltiorrhizae (RSM), a well-known traditional Chinese medicinal herb, has been used to improve blood circulation and resolve blood stasis. We have previously found that RSM has neuroprotective effect on ischemia and/ or ischemia-reperfusion rats. The purpose of this study was to obtain further information on the mechanism of the RSM-in-duced neuroprotection and to examine the neuroprotective effect on neurons exposed to anoxia. The effect of RSM on anoxic damage in cultured hippocampal neurons of neonatal rat was investigated by using morphological changes and heat shock protein 70kD (HSP70) expression as indicators. RSM given 0.5h before 2h-anoxia followed by 48 hours reoxygenation could significantly increase survival rate of hippocampal neurons and number of HSP70 positive cells. The results suggest that RSM has a direct neuroprotective effects on anoxic damage in hippocampal neurons.
文摘To explore the possibility of hydrogen sulfide (H 2S) as a messenger molecule in cardiovascular system, the authors discovered that H 2S (5×10 -5 -5×10 -4 mol·L -1 )exerted an effect on inhibiting endothelin 1 induced proliferation of cultured vascular smooth muscle cells (VSMCs) of rats in vitro . The 3H TdR incorporation decreased by 16.8%～37.4% in H 2S treated VSMCs as compared with the controls ( P <0.01). The inhibitory effect was found to be associated with reduced activity of MAPK. The authors also observed that endogenous H 2S levels markedly increased in vessels of rats with either endotoxic shock or septic shock [H 2S level (pmol·min -1 ·mg -1 ):tail artery (16.18±2.06) vs (8.12±0.55);mesenteric artery (10.17±1.11) vs (6.19 ±0.55);pulmonary artery(11.38±1.24) vs (5.27±0.51); aorta(6.21±0.48) vs (4.10± 0.28), P < 0.01 ]. The above findings suggested that H 2S might play an important role in the regulation of cardiovascular pathophysiologic events.
