scholarly journals Neuritic Beading Induced by Activated Microglia Is an Early Feature of Neuronal Dysfunction Toward Neuronal Death by Inhibition of Mitochondrial Respiration and Axonal Transport

2005 ◽  
Vol 280 (11) ◽  
pp. 10444-10454 ◽  
Author(s):  
Hideyuki Takeuchi ◽  
Tetsuya Mizuno ◽  
Guiqin Zhang ◽  
Jinyan Wang ◽  
Jun Kawanokuchi ◽  
...  
Keyword(s):  
Axonal Transport ◽  
Mitochondrial Respiration ◽  
Neuronal Death ◽  
Neuronal Dysfunction ◽  
Activated Microglia

scholarly journals Efficient propagation of misfolded tau between individual neurons occurs in absence of degeneration

2018 ◽  
Author(s):  
Grace I Hallinan ◽  
Mariana Vargas-Caballero ◽  
Jonathan West ◽  
Katrin Deinhardt
Keyword(s):  
Cell Death ◽  
Axonal Transport ◽  
Tau Protein ◽  
Neuronal Death ◽  
Early Event ◽  
Neuronal Dysfunction ◽  
Tau Pathology ◽  
Functional Consequences ◽  
Tau Aggregation ◽  
The Brain

AbstractIn Alzheimer’s disease, misfolded tau protein propagates through the brain in a prion-like manner along connected circuits. Tauopathy correlates with significant neuronal death, but the links between tau aggregation, propagation, neuronal dysfunction and death remain poorly understood, and the direct functional consequences for the neuron containing the tau aggregates are unclear. Here, by monitoring individual neurons within a minimal circuit, we demonstrate that misfolded tau efficiently spreads from presynaptic to postsynaptic neurons. Within postsynaptic cells, tau aggregates initially in distal axons, while proximal axons remain free of tau pathology. In the presence of tau aggregates neurons display axonal transport deficits, but remain viable and electrically competent. This shows that misfolded tau species are not immediately toxic to neurons, and suggests that propagation of misfolded tau is an early event in disease, occurring prior to neuronal dysfunction and cell death.

scholarly journals Reciprocal modulation of C/EBP-α and C/EBP-β by IL-13 in activated microglia prevents neuronal death

2013 ◽  
Vol 43 (11) ◽  
pp. 2854-2865 ◽  
Author(s):  
Hung Chuan Pan ◽  
Cheng Ning Yang ◽  
Yi Wen Hung ◽  
Wen Jane Lee ◽  
Hsing Ru Tien ◽  
...  
Keyword(s):  
Neuronal Death ◽  
Activated Microglia

Activated microglia are implicated in cognitive deficits, neuronal death, and successful recovery following intermittent ethanol exposure

2013 ◽  
Vol 236 ◽  
pp. 270-282 ◽  
Author(s):  
Ya-Nan Zhao ◽  
Fang Wang ◽  
Yan-Xia Fan ◽  
Guan-Fang Ping ◽  
Jing-Yu Yang ◽  
...  
Keyword(s):  
Cognitive Deficits ◽  
Neuronal Death ◽  
Ethanol Exposure ◽  
Activated Microglia ◽  
Successful Recovery

Disruption of neuronal function by soluble hyperphosphorylated tau in a Drosophila model of tauopathy

2010 ◽  
Vol 38 (2) ◽  
pp. 564-570 ◽  
Author(s):  
Catherine M. Cowan ◽  
Francis Chee ◽  
David Shepherd ◽  
Amritpal Mudher
Keyword(s):  
Axonal Transport ◽  
Neuronal Death ◽  
Synaptic Function ◽  
Hyperphosphorylated Tau ◽  
Neuronal Function ◽  
Synaptic Loss ◽  
Early Stages ◽  
Mediated Effects ◽  
Drosophila Model ◽  
Ad Alzheimer’S Disease

Axonal microtubules are essential for transport of materials to the synapse. Compromised microtubules and synaptic loss have been demonstrated in AD (Alzheimer's disease), which is believed to contribute to cognitive dysfunction before neuronal death in the early stages of the disease. The mechanism by which hyperphosphorylated tau, the building block of neurofibrillary tangles, one of the pathological hallmarks of AD, disrupts neuronal and synaptic function is unclear. There is a theory that hyperphosphorylated tau does not bind effectively to microtubules and is no longer able to function in stabilizing them, thus axonal transport can no longer proceed efficiently. This leads to synaptic dysfunction. We have tested this theory in a Drosophila model of tauopathies in which we expressed human tau (h-tau). Using this model, we have tested all aspects of this hypothesis and have demonstrated that axonal transport does become compromised in the presence of hyperphosphorylated h-tau and this leads to synaptic and behavioural defects. We are currently investigating the mechanism by which hyperphosphorylated h-tau mediates this effect and are preliminary data indicate that this entails phospho-tau-mediated effects that are predicted by the tau–microtubule hypothesis, as well as novel effects. These deleterious effects of h-tau occur in the absence of tau filaments and before neuronal death. This sequence of pathogenic events may constitute the mechanism by which abnormal tau disrupts neuronal and synaptic function and contributes to cognitive impairment before neuronal death in the early stages of tauopathies such as AD.

scholarly journals Mechanisms Underlying Neuronal Death Induced by Chromogranin A-activated Microglia

2000 ◽  
Vol 276 (16) ◽  
pp. 13113-13120 ◽  
Author(s):  
Jaroslava Ciesielski-Treska ◽  
Gabrielle Ulrich ◽  
Sylvette Chasserot-Golaz ◽  
Jean Zwiller ◽  
Marie-Odile Revel ◽  
...  
Keyword(s):  
Neuronal Death ◽  
Chromogranin A ◽  
Activated Microglia

Proinflammatory mediators released by activated microglia induces neuronal death in Japanese encephalitis

Glia ◽  
2007 ◽  
Vol 55 (5) ◽  
pp. 483-496 ◽  
Author(s):  
Ayan Ghoshal ◽  
Sulagna Das ◽  
Soumya Ghosh ◽  
Manoj Kumar Mishra ◽  
Vivek Sharma ◽  
...  
Keyword(s):  
Japanese Encephalitis ◽  
Neuronal Death ◽  
Activated Microglia ◽  
Proinflammatory Mediators

Brucella abortus-activated microglia induce neuronal death through primary phagocytosis

Glia ◽  
2017 ◽  
Vol 65 (7) ◽  
pp. 1137-1151 ◽  
Author(s):  
Ana M. Rodríguez ◽  
M. Victoria Delpino ◽  
M. Cruz Miraglia ◽  
Miriam M. Costa Franco ◽  
Paula Barrionuevo ◽  
...  
Keyword(s):  
Brucella Abortus ◽  
Neuronal Death ◽  
Activated Microglia

scholarly journals Inhibition of Soluble Epoxide Hydrolase after Cardiac Arrest/Cardiopulmonary Resuscitation Induces a Neuroprotective Phenotype in Activated Microglia and Improves Neuronal Survival

2013 ◽  
Vol 33 (10) ◽  
pp. 1574-1581 ◽  
Author(s):  
Jianming Wang ◽  
Tetsuhiro Fujiyoshi ◽  
Yasuharu Kosaka ◽  
Jonathan D Raybuck ◽  
K Matthew Lattal ◽  
...  
Keyword(s):  
Cardiac Arrest ◽  
Cardiopulmonary Resuscitation ◽  
Neuronal Death ◽  
Epoxide Hydrolase ◽  
Memory Function ◽  
Specific Treatment ◽  
Neuronal Loss ◽  
Soluble Epoxide Hydrolase ◽  
Activated Microglia ◽  
Tnf Α

Cardiac arrest (CA) causes hippocampal neuronal death that frequently leads to severe loss of memory function in survivors. No specific treatment is available to reduce neuronal death and improve functional outcome. The brain's inflammatory response to ischemia can exacerbate injury and provides a potential treatment target. We hypothesized that microglia are activated by CA and contribute to neuronal loss. We used a mouse model to determine whether pharmacologic inhibition of the proinflammatory microglial enzyme soluble epoxide hydrolase (sEH) after CA alters microglial activation and neuronal death. The sEH inhibitor 4-phenylchalcone oxide (4-PCO) was administered after successful cardiopulmonary resuscitation (CPR). The 4-PCO treatment significantly reduced neuronal death and improved memory function after CA/CPR. We found early activation of microglia and increased expression of inflammatory tumor necrosis factor (TNF)-α and interleukin (IL)-1β in the hippocampus after CA/CPR, which was unchanged after 4-PCO treatment, while expression of antiinflammatory IL-10 increased significantly. We conclude that sEH inhibition after CA/CPR can alter the transcription profile in activated microglia to selectively induce antiinflammatory and neuroprotective IL-10 and reduce subsequent neuronal death. Switching microglial gene expression toward a neuroprotective phenotype is a promising new therapeutic approach for ischemic brain injury.

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