Neuroscience
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Double transgenic mice expressing mutant amyloid precursor protein (APPswe) and mutant presenilin 1 (PS1dE9) are a model of Alzheimer-type amyloidosis and are widely used in experimental studies. In the present work, the relationships between brain and plasma amyloid-β peptide (Aβ) levels and cognitive impairments were examined in male APPswe/PS1dE9 double transgenic mice at different ages. When compared with non-transgenic littermates, APPswe/PS1dE9 mice exhibited significant learning deficits from the age of 6months (M6), which were aggravated at later stages of life (M8 and M12). ⋯ The plasma levels of Aβ40 and Aβ42 decreased with advancing age up to M8, when they stabilized at M12. This decrease in plasma Aβ levels coincided with the observed increase in insoluble brain Aβ levels. These results could be useful for developing plasma Aβ levels as possible biomarkers of the cerebral amyloidosis and provide advances in the knowledge of the Aβ peptide biochemical changes that occur in the brain of Alzheimer's disease patients.
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A main component of St. John's Wort (Hypericum perforatum, HP) is hyperforin which has antioxidant properties in dorsal root ganglion (DRG) neurons, due to its ability to modulate NADPH oxidase and protein kinase C. Recent reports indicate that oxidative stress through NADPH oxidase activates TRPM2 channels. ⋯ Glutathione peroxidase activity and GSH values in the DRG were high in HP, 2-APB and V+D groups although lipid peroxidation level was low in the groups. In conclusion, we observed a protective role for HP on Ca(2+) entry through a TRPM2 channel in the DRG neurons. Since over-production of oxidative stress and Ca(2+) entry are implicated in the pathophysiology of neuropathic pain and neuronal inflammation, our findings may be relevant to the etiology and treatment of neuropathology in DRG neurons.
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To explore the effects of modulating autophagy on neuroamyloidogenesis in an ischemic stroke model of cultured neuroblastoma 2a (N2a)/Amyloid precursor protein (APP)695 cells. ⋯ Our data suggested that down-regulating autophagy may inhibit ischemia-induced neuroamyloidogenesis via suppressing the activation of NF-κB pathway. This study might help us to find a new therapeutic strategy to prevent brain ischemic damage and depress the risk of post-stroke dementia.
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Neonatal stroke occurs in approximately 1/4000 live births and results in life-long neurological impairments: e.g., cerebral palsy. Currently, there is no evidence-based specific treatment for neonates with stroke. Several studies have reported the benefits of umbilical cord blood (UCB) cell treatment in rodent models of neonatal brain injury. ⋯ With cell treatment, the percent loss of ipsilateral hemispheric volume was significantly ameliorated (21.5±1.9%) compared with the PBS group (25.6±5.1%) when assessed at 7weeks after MCAO. The cell-treated group did not exhibit significant differences from the PBS group in either rotarod (238±46s in the sham-surgery group, 175±49s in the PBS group, 203±54s in the cell-treated group) or open-field tests. The intravenous administration of human UCB CD34(+) cells modestly reduced histological ischemic brain damage after neonatal stroke in mice, with a transient augmentation of CBF in the peri-infarct area.
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Previous studies have shown that patients with Parkinson's disease (PD) experience extensive problems during dual tasking. Up to now, dual-task interference in PD has mainly been investigated in the context of gait research. However, the simultaneous performance of two different tasks is also a prerequisite to efficiently perform many other tasks in daily life, including upper limb tasks. ⋯ In addition, there was a larger dual-task effect on the secondary task in PD patients than controls (p=0.025). The writing tests on the writing tablet proved highly correlated to daily life writing as measured by the 'Systematic Screening of Handwriting Difficulties' test (SOS-test) and other manual dexterity tasks, particularly during dual-task conditions. Taken together, these results provide additional insights into the motor control of handwriting and the effects of dual tasking during upper limb movements in patients with PD.