Papers by Natasa Dragicevic
Journal of Alzheimer's Disease, Sep 19, 2011
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Journal of Radiology Case Reports, Aug 31, 2012
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Neuropharmacology, Dec 1, 2012
Caffeine and melatonin have been shown to protect the Swedish mutant amyloid precursor protein (A... more Caffeine and melatonin have been shown to protect the Swedish mutant amyloid precursor protein (APP(sw)) transgenic mouse model of Alzheimer's disease from cognitive dysfunction. But their mechanisms of action remain incompletely understood. These Alzheimer's mice have extensive mitochondrial dysfunction, which likely contributes to their cognitive decline. To further explore the mechanism through which caffeine and melatonin protect cognitive function in these mice, we monitored the function of isolated mitochondria from APP(sw) mice treated with caffeine, melatonin, or both in their drinking water for one month. Melatonin treatment yielded a near complete restoration of mitochondrial function in assays of respiratory rate, membrane potential, reactive oxygen species production, and ATP levels. Caffeine treatment by itself yielded a small increase in mitochondrial function. However, caffeine largely blocked the large enhancement of mitochondrial function provided by melatonin. Studies with N2a neuroblastoma cells stably expressing APP(sw) showed that specific inhibition of cAMP-dependent phosphodiesterase (PDE) 4 or cGMP-dependent PDE5 also blocked melatonin protection of mitochondrial function, but A(2a) and A₁ adenosine receptor antagonists were without effect. Melatonin or caffeine at the concentrations used to modulate mitochondrial function in the cells had no effect on cAMP-dependent PDE activity or cellular cAMP or cGMP levels. Therefore, caffeine and increased cyclic nucleotide levels likely block melatonin signaling to mitochondria by independent mechanisms that do not involve adenosine receptor antagonism. The results of this study indicate that melatonin restores mitochondrial function much more potently than caffeine in APP(sw) transgenic mouse and cell models of Alzheimer's disease.
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RöFo - Fortschritte auf dem Gebiet der Röntgenstrahlen und der bildgebenden Verfahren, 2017
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The Journal of Comparative Neurology, 1989
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Neurobiology of Aging, 2012
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Neurology, 2016
Background and Objective: Metal ion dyshomeostasis is closely related to different hallmarks of n... more Background and Objective: Metal ion dyshomeostasis is closely related to different hallmarks of neurodegeneration including protein misfolding, ROS (reactive oxygen species) production, mitochondrial failure and inflammation. It was described that transition metals, when in excess, can mediate neurotoxicity. However, recent studies have reported low levels of copper, manganese and zinc leading to excitotoxicity, decrease in ATP and cytochrome c oxidase and increase in oxidative stress. Methods N2a and N2a APPsw cells were treated with 200 different metaloporphyrins including Al, Mo, Mn, Zn, Cu, Fe, Se followed by isolation of mitochondria. ROS, MMP (mitochondrial membrane potential), cytochrome-c oxidase activity, ATP levels and Ab ELISA assays resulted in three compounds selected for further studies. APP/PS1 mice received metaloporphyrins in drinking water for 30 days. Cognitive testing including spatial and non-spatial tasks was done prior and after the treatment. Cortical, hippoc...
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Neurology, 2015
Objective: To determine frequency and subtypes of CSD in right hemispheric stroke patients,lesion... more Objective: To determine frequency and subtypes of CSD in right hemispheric stroke patients,lesion site, long term cognitive impairment and region specific atrophy Background:The panoply of right hemisphere syndromes after stroke is particularly extensive. Content specific delusions associated with region specific atrophy and dementia-like clinical picture have been underreported. Methods: Cognitive stroke registry with specific attention to self-report of content specific delusions and by standardized examiner questioning. MRI NeuroQuant® software was utilized for quantification of total and subregional brain volume loss in frontal, temporal, parietal lobes and hippocampus. RESULTS: Analysis revealed 1476 patients with ischemic stroke, 354 right hemisphere lesions and 407 with left hemisphere lesions. Analysis of CSD with right hemisphere lesions in 272 patients after exclusion of 82 patients with coma or encephalopathy, revealed 31 (11[percnt]) instances of CSD mean age 68.3 years ...
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Objective: Aim of present study was to investigate effects of synthetic metalloporphyrins alone a... more Objective: Aim of present study was to investigate effects of synthetic metalloporphyrins alone and porphyrins with resveratrol on mitochondrial function, cognitive performance and total and mitochondrial amyloid-beta levels in Alzheimer’s mice. Background: Metalloporphyrins, characterized by a redox-active transitional metal coordinated to a cyclic porphyrin core ligand, mitigate oxidative/nitrosative stress in biological systems. Resveratrol is a polyphenol acting as a neuroprotectant by modulating Aβ pathomechanisms through anti- apoptotic, anti-oxidative stress, and anti-neuroinflammatory effects. Design/Methods: APP/PS-1 mice were treated with synthetic porphyrins (Co, Mn and Zn) alone or porphyrin + resveratrol for 90 days, followed by isolation of mitochondria from cortex, hippocampus and amygdala. Reactive Oxygen Species (ROS), MMP (mitochondrial membrane potential), cytochrome-c oxidase activity, ATP levels and Ab ELISA assays were performed. Behavioral testing was performe...
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Radiology Case Reports
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Journal of Radiology Case Reports, 2012
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Emergency Radiology, 2010
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Papers by Natasa Dragicevic