Journal of molecular neuroscience : MN
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Curcumin (Cur) is a major active component of the food flavor turmeric isolated from the powdered dry rhizome of Curcuma longa Linn., which has been used in traditional Chinese medicine to ameliorate intracerebral ischemic damage and reduce brain edema. However, the effects of Cur on the disruption of the blood-brain barrier (BBB) induced by brain ischemia are still unclear. The effects of Cur on the disruption of BBB and changes of tight junction (TJ) proteins induced by oxygen glucose deprivation (OGD) were studied in BBB in vitro. ⋯ After administration of OGD, the expression of occludin and ZO-1 proteins was restored by Cur, and this effect was blocked by a HO-1 inhibitor, zinc protoporphyrin (ZnPP). Cur protects RBMECs against OGD-induced disruption of TJ and barrier dysfunction via the HO-1 pathway. We propose that Cur is capable of improving the barrier function of BBB under ischemic conditions and this beneficial effect might be reversed by a HO-1 inhibitor, ZnPP.
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The protein L-isoaspartyl methyltransferase (PIMT) repairs damaged aspartyl residues in proteins. It is commonly described as a cytosolic protein highly expressed in brain tissues. Here, we report that PIMT is an active monomeric as well as a multimeric protein in mitochondria isolated from neuroblastoma cells. ⋯ This indicated that PIMT monomers have lower enzymatic activity following CCCP treatments and that activation of PIMT multimers is essentially dependent on the formation of disulfide-linked monomers of PIMT. Furthermore, the perturbation of mitochondrial function by CCCP promoted the accumulation of damaged aspartyl residues in proteins with high molecular weights. Thus, this study demonstrates the formation of active PIMT multimers associated with mitochondria that could play a key role in repairing damaged proteins accumulating during mitochondrial dysfunction.
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Alzheimer's disease (AD) is a neurodegenerative disorder characterized by extracellular accumulation of amyloid deposits. Brain-derived neurotrophic factor (BDNF) is a neurotrophic factor whose levels have been shown to be decreased in AD brains. BDNF supplementation can offer improvement in the course of AD. ⋯ However, the BDNF group NAA level was still lower than the control group at 6 weeks after infusion. These changes correlated with increased immunoreactivity for TrkB, decreased compact Aβ peptide containing plaques, and decreased Fluoro-Jade B-positive cells in the BDNF-infused mice compared to vehicle controls. These findings demonstrate that 1H-MRS may be a promising means of evaluating the therapeutic effects of BDNF on AD.
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Oxidative stress leading to retinal nerve cells (RNCs) apoptosis is a major cause of neurodegenerative disorders of the retina. 17β-Estradiol (E2) has been suggested to be a neuroprotective agent in the central nervous system; however, at present, the underlying mechanisms are not well understood, and the related research on the RNCs is less reported. Here, in order to investigate the protective role and mechanism of E2 against oxidative stress-induced damage on RNCs, the transmission electron microscopy and annexin V-FITC/propidium iodide assay were applied to detect the RNCs apoptosis. Western blot and real-time PCR were used to determine the expression of the critical molecules in Bcl-2 and caspase family associated with apoptosis. ⋯ Moreover, LY294002, a phosphatidylinositol 3-kinase (PI3K) inhibitor, could sharply block the effect of E2 in reducing the percentage of apoptotic cells resistance to H(2)O(2). And the attenuation of Bax, the reduced activities of caspases 9/3 and the impeded release of mitochondrial cytochrome c mediated by E2 resistance to H(2)O(2) damage were significantly retrieved by LY294002 administration. Taken together, E2 protects the RNCs against H(2)O(2)-induced apoptosis by significantly inhibiting the Bax-involved mitochondrial apoptosis via the activation of PI3K/Akt signal pathway.
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Either sleep deprivation or Western diet can impair learning and memory via induction of oxidative stress, which results in neuronal damage and interference with the neurotransmission. In this study, we examined the combined effect of sleep deprivation and Western diet on hippocampus-dependent spatial learning and memory. In addition, possible molecular targets for sleep deprivation and Western diet-induced cognitive impairments were investigated. ⋯ In addition, the combined treatment reduced the levels of hippocampal BDNF, a reduction that was not detected with each factor alone. Moreover, the combined treatment reduced the hippocampal activities of SOD, catalase, GPx, ratio of GSH/GSSG, and elevated TBARS level (P < 0.05). In conclusion, the combination of sleep deprivation and Western diet decreases BDNF levels and increases oxidative stress in the hippocampus, thus inducing memory impairment that is greater than the impairment produced by each factor alone.