Neuroscience
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The relationship of cognitive reserve and measures of reserve with longitudinal cognitive change and the duration of preclinical, prodromal, and mild Alzheimer disease (AD) dementia remains to be fully characterized. In our study, 660 β-amyloid-positive participants staged with preclinical AD, prodromal AD, and dementia due to AD from the Alzheimer's Disease Neuroimaging Initiative were selected. Cognitive reserve and brain reserve were defined by conventional proxies or the residual method at baseline. ⋯ The estimated time from preclinical to mild AD dementia varied from 15-24 years based on the different reserve groups, and we observed a linear trend for the longest duration in individuals with high cognitive reserve/high brain reserve, followed by those with high cognitive reserve/low brain reserve, low cognitive reserve/high brain reserve, and low cognitive reserve/low brain reserve. This study showed a reduced risk of cognitive decline for individuals with higher level of reserve regardless of methods for measuring reserve. Interindividual differences in reserve may be important for clinical practice and trial design.
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Autoantibodies to neuronal antigens are viewed as potential biomarkers for neurodegenerative diseases. Increasing evidence, however, suggests a dissociation of the neurodegenerative process in the central nervous system and dynamics of neuronal proteins in peripheral circulation with the prevalence of a wide variety of immunoglobulins reactive to neuronal antigens reported also in the blood of healthy subjects, including children. Recently discovered physiological turnover of neurons in enteric nervous system with release of neuronal proteins in peripheral circulation may account for this conundrum and provide a new perspective on molecular biomarkers of neurodegenerative diseases and immunotherapy.
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The mismatch negativity (MMN) component of the human event-related potential (ERP) is frequently interpreted as a sensory prediction-error signal. However, there is ambiguity concerning the neurophysiology underlying hypothetical prediction and prediction-error signalling components, and whether these can be dissociated from overlapping obligatory components of the ERP that are sensitive to physical properties of sounds. In the present study, a hierarchical recurrent neural network (RNN) was fitted to ERP data from 38 subjects. ⋯ Hidden units were categorised according to their temporal response fields, and statistically significant differences among stimulus conditions were observed for amplitudes of units peaking in the 0-75 ms (P50), 75-125 ms (N1), and 250-400 ms (N3) latency ranges, surprisingly not including the measurement window of MMN. The model demonstrated opposite polarity changes in MMN amplitude produced by falling (70 dB) and rising (90 dB) intensity deviant stimuli, consistent with loudness dependence of sensory ERP components. This modelling study suggests that loudness dependence is a principal driver of intensity MMN, and future studies ought to clarify the distinction between loudness dependence, adaptation and prediction-error signalling.
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DJ-1 plays a neuroprotective role in cerebral ischemia- reperfusion (I/R) injury and participates in the apoptosis of brain nerve cells, but the underlying mechanism is unclear. We explored the molecular pathways underlying this role using in vivo and in vitro approaches. Middle cerebral artery occlusion- reperfusion (MCAO/R) rat models and oxygen- glucose deprivation- reoxygenation (OGD/R) HAPI cell cultures were used to simulate cerebral ischemia-reperfusion injury. ⋯ In vitro, the Notch1 signaling pathway inhibitor DAPT reversed the neuroprotective effect of ND-13 and promoted apoptosis, weakened the interaction between DJ-1 and Notch1, and decreased the expression of proteins in the Notch1 and Nrf2 pathways. Thus, we found that DJ-1 inhibits apoptosis by regulating the Notch1 signaling pathway and Nrf2 expression in cerebral I/R injury. These results imply that DJ-1 is a potential therapeutic target for cerebral I/R injury.
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Epilepsy is a neurological disorder caused by abnormally elevated neuronal firing and excitability. Spire2, also known as the nucleating factor of F-actin, plays an important role in long-range vesicle transport. This study showed that Spire2 was highly expressed in neurons in the cortex and hippocampus. ⋯ In conclusion, this study revealed a significantly decreased expression of Spire2 in the brain tissues of epileptic individuals and an inhibitory role for this protein in the development of epilepsy. In addition, knockdown of Spire2 aggravated abnormal firing in epileptic mice, while its overexpression had the opposite effect. These findings provide new insights into the mechanism of epileptogenesis.