Neuroscience
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Neurodegenerative disorders, including Amyotrophic Lateral Sclerosis (ALS), have been associated to alterations in chromatin structure resulting in long-lasting changes in gene expression. ALS is predominantly a sporadic disease and environmental triggers may be involved in its onset. ⋯ In this paper, we demonstrate that two modifications associated with transcriptional activation, namely dimethylation of lysine 4 on H3 tail (H3K4me2) and phospho-acetylation of serine 10 and lysine 14 on H3 tail (H3K14ac-S10ph), and two modifications associated to transcriptional repression, namely trimethylation of lysine 9 on H3 tail (H3K9me3) and DNA methylation are selectively altered in cellular and animal model of ALS. These results reinforce the idea that epigenetic therapy may represent a potential and attractive approach for ALS treatment.
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MK-801, a non-competitive NMDA receptor (NMDAR) antagonist, disturbs NMDAR function in rodents and induces psychological and behavioral changes similar to schizophrenia (SCZ). However, the effects of MK-801 treatment on gene expression are largely unknown. Here we performed RNA-sequencing on the prefrontal cortex of MK-801-exposed male mice in order to analyze gene expression and co-expression patterns related to SCZ and to identify mechanisms that underlie the molecular etiology of this disorder. ⋯ When combined with analyses using DAVID and STRING databases, we found that co-expression patterns were altered in synapse-related genes and genes central to the mitochondrial network. Abnormal co-expression of genes mediating synaptic vesicle cycling could disturb release, uptake and reuptake of glutamate, and the perturbation in co-expression patterns for mitochondrial respiratory chain complexes was extensive. Our study supports the hypothesis that research using MK-801-exposed male mice as an animal model of SCZ offers important insights into the pathogenesis of SCZ.
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Meta Analysis
Effect of Mirror Therapy on Recovery of Stroke Survivors: A Systematic Review and Network Meta-analysis.
Mirror therapy (MT) as a relatively new rehabilitation technique has been widely applied in stroke patients. A number of randomized controlled trials (RCTs) have investigated the effects of MT for stroke survivors. The main purpose of this network meta-analysis was to investigate the effects of MT on motor function, activities of daily living (ADL), and pain perception in stroke survivors. ⋯ Network meta-analysis showed that MT combined with electrical stimulation (ES) for less than 4 weeks along with conventional rehabilitation therapy (CT), and MT accompanied with CT for less than 4 weeks might be the most suitable interventions for improvement of motor function and ADL, respectively. Overall, MT could effectively improve motor function and ADL, as well as relieve pain for stroke survivors. The study was registered at PROSPERO (CRD42017081742).
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The insulin/insulin-like growth factor 1 (IGF1) signaling pathways are implicated in longevity and in progression of Alzheimer's disease. Previously, we showed that insulin-like growth factor 1 receptor (IGF1R) and downstream signaling transcripts are reduced in astrocytes in human brain with progression of Alzheimer's neuropathology and developed a model of IGF1 signaling impairment in human astrocytes using an IGF1R-specific monoclonal antibody, MAB391. Here, we have established a novel human astrocyte-neuron co-culture system to determine whether loss of astrocytic IGF1R affects their support for neurons. ⋯ Changes in transcripts involved in astrocyte energy metabolism were identified, particularly NDUFA2 and NDUFB6, which are related to complex I assembly. Loss of complex I activity in MAB391-treated astrocytes validated these findings. In conclusion, reduced IGF1 signaling in astrocytes impairs their support for neurons under conditions of stress and this is associated with defects in the mitochondrial respiratory chain in astrocytes.
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Blind individuals display superior sensory abilities in other modalities, yet results remain contradictory regarding their performance on olfactory tasks. Using complex ecological olfactory tasks, we evaluated the impact of blindness on olfactory performance. We tested 12 early-blind individuals (M = 49, SD = 13.09) and 12 sighted controls (M = 49, SD = 14.31) who were all blindfolded. ⋯ In summary, early-blind individuals had a harder time to categorize wine odors. This could be explained by a different construction of internal reference categories for wine in early-blind individuals. Finally, this research is in line with the notion of the absence of higher olfactory sensitivity in blind individuals.