Neuroscience
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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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We aimed to investigate the role of dorsal and ventral visual systems in rapid naming of simple Chinese characters. Twenty college students (10 female; Mage = 22.5 years) were required to covertly read a character- and a cross-matrix during an fMRI experiment. A basic prosaccade and a prosaccade-naming task were also performed to confirm the functional significance of the findings. ⋯ Moreover, in the character-matrix reading, we found a negative correlation between the reaction time of naming in the prosaccade-naming task and the EC strength from visual word form area to superior temporal gyrus and a positive correlation between the reaction time in the basic prosaccade task and the EC strength from middle frontal gyrus to intraparietal sulcus. The cross-matrix scanning did not show any brain-behavior relationship. These results suggest that while the dorsal visual system is mainly engaged in eye-movement control, the ventral system is associated more with orthographic processing and orthography-phonology mapping.
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Retinal ganglion cell axons of the DBA/2J mouse model of glaucoma, a model characterized by extensive neuroinflammation, preserve synaptic contacts with their subcortical targets for a time after onset of anterograde axonal transport deficits, axon terminal hypertrophy, and cytoskeletal alterations. Though retrograde axonal transport is still evident in these axons, it is unknown if they retain their ability to transmit visual information to the brain. Using a combination of in vivo multiunit electrophysiology, neuronal tract tracing, multichannel immunofluorescence, and transmission electron microscopy, we report that eye-brain signaling deficits precede transport loss and axonal degeneration in the DBA/2J retinal projection. ⋯ In contrast to these findings in DBA/2J mice, node pathologies were not observed in the induced microbead occlusion model of glaucoma - a model that lacks pre-existing inflammation. After one week of systemic treatment with fingolimod, an immunosuppressant therapy for relapsing-remitting MS, DBA/2J mice showed a substantial reduction in node pathology and mild effects on axon morphology. These data suggest that neurophysiological deficits in the DBA/2J may be due to defects in intact axons and targeting node pathology may be a promising intervention for some types of glaucoma.
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The promotion of angiogenesis is a promising therapeutic strategy for ischemic stroke. Many long noncoding RNAs (lncRNAs) are related to angiogenesis following ischemic stroke. LncRNA small nucleolar RNA host gene 12 (SNHG12) was upregulated in oxygen-glucose deprivation (OGD)-exposed primary brain microvascular endothelial cells and in microvessel from middle cerebral artery occlusion (MCAO) animal brains. ⋯ Furthermore, we found that SNHG12 functioned as a competing endogenous RNA for miR-150 to regulate VEGF expression. Additionally, overexpression of SNHG12 improved the recovery of neurological function, reduced infarct volume and miR-150 expression, increased vascular density and VEGF expression in the infarct border zone of MCAO mice. In conclusion, SNHG12 promotes the angiogenesis following ischemic stroke via miR-150/VEGF pathway, which further clarified the mechanism of angiogenesis after ischemic stroke and provides a target for the treatment of this disease.
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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.