scholarly journals Postsynaptic SDC2 induces transsynaptic signaling via FGF22 for bidirectional synaptic formation

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Hsiao-Tang Hu ◽  
Hisashi Umemori ◽  
Yi-Ping Hsueh
Keyword(s):  
Synaptic Formation ◽  
Transsynaptic Signaling

Neurotransplantation Therapy and Cerebellar Reserve

2018 ◽  
Vol 17 (3) ◽  
pp. 172-183 ◽  
Author(s):  
Jan Cendelin ◽  
Hiroshi Mitoma ◽  
Mario Manto
Keyword(s):  
Neural Plasticity ◽  
Clinical Evidence ◽  
The Self ◽  
Regenerative Processes ◽  
Recovery Capacity ◽  
Cerebellar Ataxias ◽  
Synaptic Formation ◽  
Target Recovery ◽  
Cerebellar Anatomy ◽  
Functional Circuitry

Background & Objective: Neurotransplantation has been recently the focus of interest as a promising therapy to substitute lost cerebellar neurons and improve cerebellar ataxias. However, since cell differentiation and synaptic formation are required to obtain a functional circuitry, highly integrated reproduction of cerebellar anatomy is not a simple process. Rather than a genuine replacement, recent studies have shown that grafted cells rescue surviving cells from neurodegeneration by exerting trophic effects, supporting mitochondrial function, modulating neuroinflammation, stimulating endogenous regenerative processes, and facilitating cerebellar compensatory properties thanks to neural plasticity. On the other hand, accumulating clinical evidence suggests that the self-recovery capacity is still preserved even if the cerebellum is affected by a diffuse and progressive pathology. We put forward the period with intact recovery capacity as “restorable stage” and the notion of reversal capacity as “cerebellar reserve”. Conclusion: The concept of cerebellar reserve is particularly relevant, both theoretically and practically, to target recovery of cerebellar deficits by neurotransplantation. Reinforcing the cerebellar reserve and prolonging the restorable stage can be envisioned as future endpoints of neurotransplantation.

scholarly journals Thrombopoietin Receptor Agonist Eltrombopag Prevents Insulin Resistance and Synaptic Pathology via HIF1α/COX2/Sirt1 Signaling Pathway 

2021 ◽  
Author(s):  
he yu ◽  
xuebao wang ◽  
leping liu ◽  
baihui chen ◽  
shuya feng ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Learning And Memory ◽  
Receptor Agonist ◽  
Synaptic Activity ◽  
Sirtuin 1 ◽  
High Dose ◽  
Thrombopoietin Receptor ◽  
Thrombopoietin Receptor Agonist ◽  
Synaptic Formation

Abstract Background: Insulin resistance has been reported to be closely correlated with the pathogenesis of MHE. The mechanism underlying the effects of thrombopoietin receptor agonist eltrombopag (ELT) on synaptic activity and formation involved in MHE pathogenesis remains unclear. Methods: The effect of ELT on neurodegeneration and insulin resistance was examined in the primary rat neurons and an MHE rat model. Results: We found that the level of thrombopoietin receptor c-MPL (MPL) expression was decreased in MHE brains, and ELT administration improved insulin resistance, alleviated the destruction of synaptic formation and enhanced learning and memory in the MHE rats, indicating the relationship between dowregulated ELT and insulin resistance. Then in vitro, ELT treatment ameliorated the impairment of glucose uptake, indicating the reduction of insulin resistance. High dose of glucose inhibited insulin-stimulated downregulation of Hypoxia-inducible factor-1α (HIF1α) expression, the inhibition of inflammatory response and upregulation of sirtuin-1 (Sirt1), destruction of synaptic formation and activity, which were all reversed by ELT treatment in insulin resistant neurons.Conclusions: These results indicate that ELT is a promising potential therapeutic agent for insulin resistance and defect in learning and memory.

scholarly journals Neuronal control of astrocytic respiration through a variant of the Crabtree effect

2018 ◽  
Vol 115 (7) ◽  
pp. 1623-1628 ◽  
Author(s):  
Ignacio Fernández-Moncada ◽  
Iván Ruminot ◽  
Daniel Robles-Maldonado ◽  
Karin Alegría ◽  
Joachim W. Deitmer ◽  
...  
Keyword(s):  
Energy Demand ◽  
Aerobic Glycolysis ◽  
Hippocampal Slices ◽  
Energetic Efficiency ◽  
Crabtree Effect ◽  
Proliferating Cells ◽  
Neuronal Control ◽  
Synaptic Formation ◽  
Oxygen Measurements

Aerobic glycolysis is a phenomenon that in the long term contributes to synaptic formation and growth, is reduced by normal aging, and correlates with amyloid beta deposition. Aerobic glycolysis starts within seconds of neural activity and it is not obvious why energetic efficiency should be compromised precisely when energy demand is highest. Using genetically encoded FRET nanosensors and real-time oxygen measurements in culture and in hippocampal slices, we show here that astrocytes respond to physiological extracellular K+ with an acute rise in cytosolic ATP and a parallel inhibition of oxygen consumption, explained by glycolytic stimulation via the Na+-bicarbonate cotransporter NBCe1. This control of mitochondrial respiration via glycolysis modulation is reminiscent of a phenomenon previously described in proliferating cells, known as the Crabtree effect. Fast brain aerobic glycolysis may be interpreted as a strategy whereby neurons manipulate neighboring astrocytes to obtain oxygen, thus maximizing information processing.

scholarly journals Chronic Unexpected Mild Stress Destroys Synaptic Plasticity of Neurons through a Glutamate Transporter, GLT-1, of Astrocytes in the Ischemic Stroke Rat

2019 ◽  
Vol 2019 ◽  
pp. 1-13 ◽  
Author(s):  
Dafan Yu ◽  
Zhenxing Cheng ◽  
Abdoulaye Idriss Ali ◽  
Jiamin Wang ◽  
Kai Le ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Synaptic Plasticity ◽  
Dentate Gyrus ◽  
Average Distance ◽  
Glutamate Transporter ◽  
Synaptic Cleft ◽  
Mild Stress ◽  
Poststroke Depression ◽  
Transmission Electron ◽  
Synaptic Formation

Background and Objective. Chronic unexpected mild stress (CUMS) destroys synaptic plasticity of hippocampal regenerated neurons that may be involved in the occurrence of poststroke depression. Astrocytes uptake glutamate at the synapse and provide metabolic support for neighboring neurons. Currently, we aim to investigate whether CUMS inhibits synaptic formation of regenerated neurons through a glutamate transporter, GLT-1, of astrocytes in the ischemic stroke rats. Method. We exposed the ischemic stroke rats to ceftriaxone, during the CUMS intervention period to determine the effects of GLT-1 on glutamate circulation by immunofluorescence and mass spectrometry and its influences to synaptic plasticity by western blot and transmission electron microscopy. Result. CUMS evidently reduced the level of astroglial GLT-1 in the hippocampus of the ischemic rats (p<0.05), resulting in smaller amount of glutamate being transported into astrocytes surrounding synapses (p<0.05), and then expression of synaptophysin was suppressed (p<0.05) in hippocampal dentate gyrus. The ultrastructures of synapses in dentate gyrus were adversely influenced including decreased proportion of smile synapses, shortened thickness of postsynaptic density, reduced number of vesicles, and widened average distance of the synaptic cleft (all p<0.05). Moreover, ceftriaxone can promote glutamate circulation and synaptic plasticity (all p<0.05) by raising astroglial GLT-1 (p<0.05) and then improve depressive behaviors of the CUMS-induced model rats (p<0.05). Conclusion. Our study shows that CUMS destroys synaptic plasticity of regenerated neurons in the hippocampus through a glutamate transporter, GLT-1, of astrocytes in the ischemic stroke rats. This may indicate one potential pathogenesis of poststroke depression.

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