Neuroscience
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PTPN11 is associated with regulation of growth factor signaling pathways in neuronal cells. Using SH-SY5Y neuroblastoma cells, we showed that adeno-associated virus (AAV)-mediated PTPN11 upregulation was associated with TrkB antagonism, reduced neuritogenesis and enhanced endoplasmic reticulum (ER) stress response leading to apoptotic changes. Genetic knock-down of PTPN11 on the other hand leads to increased TrkB phosphorylation in SH-SY5Y cells. ⋯ This study provides evidence of molecular interactions between PTPN11 and the TrkB receptor in SH-SY5Y cells. The results reinforce the role played by PTPN11 in regulating neurotrophin protective signaling in neuronal cells and highlight that PTPN11 dysregulation promotes apoptotic activation. Based on these findings we suggest that blocking PTPN11 could have potential beneficial effects to limit the progression of neuronal loss in neurodegenerative disorders.
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Local lesions caused by stroke may result in extensive structural and functional reorganization in the brain. Previous studies of this phenomenon have focused on specific brain networks. Here, we aimed to discover abnormalities in whole-brain networks and to explore the decoupling between structural and functional connectivity in patients with stroke. ⋯ Positive correlations between the nodal degree of the inferior parietal lobule and the Fugl-Meyer Assessment (FMA) score and between the nodal betweenness centrality of the posterior cingulate gyrus (PCG) and immediate recall were observed in patients with stroke. Most importantly, the strength of the structural-functional connectivity network coupling was decreased, and the coupling degree was related to the FMA score of patients, suggesting that decoupling may provide a novel biomarker for the assessment of motor impairment in patients with stroke. Thus, the topological organization of brain networks is altered in patients with stroke, and our results provide insights into the structural and functional organization of the brain after stroke from the viewpoint of network topology.
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Neurogenesis in the subventricular zone (SVZ) plays a vital role in neurologic recovery after stroke. However, only a small fraction of newly generated neuroblasts from the SVZ will survive long-term. Successful migration and survival of neuroblasts requires angiogenesis, lesion-derived chemo-attractants, and appropriate local microenvironments, which are partly regulated by the platelet-derived growth factor receptor (PDGFR) signaling pathway. ⋯ Crenolanib treatment increased the apoptosis of pericytes and decreased the pericyte/vascular coverage, but had no effects on apoptosis of astrocytes. We conclude that the PDGFR signaling pathway plays a vital role in the SVZ neurogenesis after stroke. It can also affect angiogenesis, lesion-derived chemo-attractants, and the local microenvironment, which are all important to stroke-induced neurogenesis.
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Secondary neuronal degeneration (SND) occurring in Traumatic brain injury (TBI) consists in downstream destructive events affecting cells that were not or only marginally affected by the initial wound, further increasing the effects of the primary injury. Glutamate excitotoxicity is hypothesized to play an important role in SND. TBI is a common cause of olfactory dysfunction that may be spontaneous and partially recovered. ⋯ A lack of correlation between OB volumes and olfactory function was observed. An increase in SVZ neurogenesis (Ki67+ cells, PSANCAM+ cells (p<0.01) associated with an increase in OB glomerular dopaminergic immunostaining (p<0.05) were related to olfactory function recovery. The present results show that changes in OB volumes cannot explain the recovery of the olfactory function and suggest a relevant role for dopaminergic OB interneurons in the pathophysiology of recovery of loss of smell in TBI.
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Neurons coding spatial location (grid cells) are found in medial entorhinal cortex (MEC) and demonstrate increasing size of firing fields and spacing between fields (grid scale) along the dorsoventral axis. This change in grid scale correlates with differences in theta frequency, a 6-10Hz rhythm in the local field potential (LFP) and rhythmic firing of cells. A relationship between theta frequency and grid scale can be found when examining grid cells recorded in different locations along the dorsoventral axis of MEC. ⋯ All known anxiolytic drugs decrease hippocampal theta frequency despite their differing mechanisms of action. Specifically, anxiolytics decrease the intercept of the theta frequency-running speed relationship in the hippocampus. Here we demonstrate that anxiolytics decrease the intercept of the theta frequency-running speed relationship in the MEC, similar to hippocampus, and the decrease in frequency through this change in intercept does not affect grid scale.