Nitric oxide （NO） has been implicated in the promotion of neurodegeneration. However, little is known about the relationship between NO and the self-renewal or differentiation capacity of neural stem cells （NSCs） ...Nitric oxide （NO） has been implicated in the promotion of neurodegeneration. However, little is known about the relationship between NO and the self-renewal or differentiation capacity of neural stem cells （NSCs） in neurodegenerative disease. In this study, we investigated the effect of NO on self-renewal of NSCs in an animal model for Niemann-Pick type C （NPC） disease. We found that NO production was significantly increased in NSCs from NPCl-deficient mice （NPCI^-/-）, which showed reduced NSC self-renewal. The number of nestin-positive cells and the size of neurospheres were both significantly decreased. The expression of NO synthase （NOS） was increased in neurospheres derived from the brain of NPC1^-/- mice in comparison to wild-type neurospheres. NO-mediated activation of glycogen synthase ki- nase-3β （GSK3β） and caspase-3 was also observed in NSCs from NPC1^-/- mice. The self-renewal ability of NSCs from NPC1^-/- mice was restored by an NOS inhibitor, L-NAME, which resulted in the inhibition of GSK3β and caspase-3. In addition, the differentiation ability of NSCs was partially restored and the number of Fluoro-Jade C-positive degenerating neurons was reduced. These data suggest that overproduction of NO in NPC disease impaired the self-renewal of NSCs. Control of NO production may be key for the treatment of NPC disease.展开更多
Astrocytes can release increased levels of brain-derived neurotrophic factor during cerebral ischemia, but it is unclear whether brain-derived neurotrophic factor affects y-aminobutyric acid type A receptor function i...Astrocytes can release increased levels of brain-derived neurotrophic factor during cerebral ischemia, but it is unclear whether brain-derived neurotrophic factor affects y-aminobutyric acid type A receptor function in normal neurons. Results from this study demonstrated that y-aminobutyric acid at 100 pmol/L concentration raised the intracellular calcium level in neurons treated with medium from cultured hypoxic astrocytes, and the rise in calcium level could be inhibited by y-aminobutyric acid type A receptor antagonist bicuculline or brain-derived neurotrophic factor receptor antagonist k252a, y-aminobutyric acid type A-gated current induced by 100 IJmol/L y-aminobutyric acid was in an inward direction in physiological conditions, but shifted to the outward direction in neurons when treated with the medium from cultured hypoxic astrocytes, and this effect could be inhibited by k252a. The reverse potential was shifted leftward to -93 mV, which could be inhibited by k252a and Na＋-K＋-CI cotransporter inhibitor bumetanide. Brain-derived neurotrophic factor was released from hypoxic astrocytes at a high level. It shifted the reverse potential of y-aminobutyric acid type A-gated currents leftward in normal neurons by enhancing the function of Na＋-K＋-CI- cotransporter, and caused y-aminobutyric acid to exert an excitatory effect by activating y-aminobutyric acid type A receptor.展开更多
This paper proposes a simple constant-stress accel- erated life test （ALT） model from Burr type XII distribution when the data are Type-I progressively hybrid censored. The maximum likelihood estimation （MLE） of t...This paper proposes a simple constant-stress accel- erated life test （ALT） model from Burr type XII distribution when the data are Type-I progressively hybrid censored. The maximum likelihood estimation （MLE） of the parameters is obtained through the numerical method for solving the likelihood equations. Approxi- mate confidence interval （CI）, based on normal approximation to the asymptotic distribution of MLE and percentile bootstrap Cl is derived. Finally, a numerical example is introduced and then a Monte Carlo simulation study is carried out to illustrate the pro- posed method.展开更多
文摘Nitric oxide （NO） has been implicated in the promotion of neurodegeneration. However, little is known about the relationship between NO and the self-renewal or differentiation capacity of neural stem cells （NSCs） in neurodegenerative disease. In this study, we investigated the effect of NO on self-renewal of NSCs in an animal model for Niemann-Pick type C （NPC） disease. We found that NO production was significantly increased in NSCs from NPCl-deficient mice （NPCI^-/-）, which showed reduced NSC self-renewal. The number of nestin-positive cells and the size of neurospheres were both significantly decreased. The expression of NO synthase （NOS） was increased in neurospheres derived from the brain of NPC1^-/- mice in comparison to wild-type neurospheres. NO-mediated activation of glycogen synthase ki- nase-3β （GSK3β） and caspase-3 was also observed in NSCs from NPC1^-/- mice. The self-renewal ability of NSCs from NPC1^-/- mice was restored by an NOS inhibitor, L-NAME, which resulted in the inhibition of GSK3β and caspase-3. In addition, the differentiation ability of NSCs was partially restored and the number of Fluoro-Jade C-positive degenerating neurons was reduced. These data suggest that overproduction of NO in NPC disease impaired the self-renewal of NSCs. Control of NO production may be key for the treatment of NPC disease.
基金the National Natural Science Foundation of China, No. 30471657
文摘Astrocytes can release increased levels of brain-derived neurotrophic factor during cerebral ischemia, but it is unclear whether brain-derived neurotrophic factor affects y-aminobutyric acid type A receptor function in normal neurons. Results from this study demonstrated that y-aminobutyric acid at 100 pmol/L concentration raised the intracellular calcium level in neurons treated with medium from cultured hypoxic astrocytes, and the rise in calcium level could be inhibited by y-aminobutyric acid type A receptor antagonist bicuculline or brain-derived neurotrophic factor receptor antagonist k252a, y-aminobutyric acid type A-gated current induced by 100 IJmol/L y-aminobutyric acid was in an inward direction in physiological conditions, but shifted to the outward direction in neurons when treated with the medium from cultured hypoxic astrocytes, and this effect could be inhibited by k252a. The reverse potential was shifted leftward to -93 mV, which could be inhibited by k252a and Na＋-K＋-CI cotransporter inhibitor bumetanide. Brain-derived neurotrophic factor was released from hypoxic astrocytes at a high level. It shifted the reverse potential of y-aminobutyric acid type A-gated currents leftward in normal neurons by enhancing the function of Na＋-K＋-CI- cotransporter, and caused y-aminobutyric acid to exert an excitatory effect by activating y-aminobutyric acid type A receptor.
基金supported by the National Natural Science Foundation of China(7117116470471057)
文摘This paper proposes a simple constant-stress accel- erated life test （ALT） model from Burr type XII distribution when the data are Type-I progressively hybrid censored. The maximum likelihood estimation （MLE） of the parameters is obtained through the numerical method for solving the likelihood equations. Approxi- mate confidence interval （CI）, based on normal approximation to the asymptotic distribution of MLE and percentile bootstrap Cl is derived. Finally, a numerical example is introduced and then a Monte Carlo simulation study is carried out to illustrate the pro- posed method.
