Icariin Inhibits the Increased Inward Calcium Currents Induced by Amyloid-β25-35 Peptide in CA1 Pyramidal Neurons of Neonatal Rat Hippocampal Slice

2010 ◽  
Vol 38 (01) ◽  
pp. 113-125 ◽  
Author(s):  
Li Li ◽  
Hao-Jan Tsai ◽  
Lin Li ◽  
Xue-Mei Wang
Keyword(s):  
Intracellular Calcium ◽  
Calcium Homeostasis ◽  
Pyramidal Neurons ◽  
Neuronal Damage ◽  
Neuroprotective Effect ◽  
Amyloid Β ◽  
Calcium Currents ◽  
Neonatal Rat ◽  
Amyloid Β Peptide ◽  
Hippocampal Pyramidal Neurons

Overload of intracellular calcium caused by amyloid-β peptide has been implicated in the pathogenesis of neuronal damage in Alzheimer's disease. Voltage-gated calcium channels (VGCCs) provide one of the major sources of Ca2+ entry into cells. Here, we investigated whether icariin had effect on the changes of calcium currents induced by Aβ25-35 in hippocampal pyramidal neurons. Using whole-cell patch-clamp, we showed that Aβ25-35 enhanced the inward Ba2+ and Ca2+ currents. The currents were partially inhibited by Ni2+ and completely suppressed by Cd2+ , indicating that Aβ25-35 disrupts intracellular calcium homeostasis via the modulation of both L- and T-type channels. Furthermore, icariin nearly complete suppressed the abnormal inward calcium currents induced by Aβ25-35 in a dose-dependant manner. Our findings suggest that the potential neuroprotective effect of icariin on Aβ25-35-induced neurotoxicity via the balance intracelluar calcium homeostasis.

Val8-GLP-1 remodels synaptic activity and intracellular calcium homeostasis impaired by amyloid β peptide in rats

2013 ◽  
Vol 91 (4) ◽  
pp. 568-577 ◽  
Author(s):  
Xiao-Hui Wang ◽  
Wei Yang ◽  
Christian Hölscher ◽  
Zhao-Jun Wang ◽  
Hong-Yan Cai ◽  
...  
Keyword(s):  
Intracellular Calcium ◽  
Calcium Homeostasis ◽  
Amyloid Β ◽  
Synaptic Activity ◽  
Amyloid Β Peptide ◽  
Intracellular Calcium Homeostasis

scholarly journals APP processing is regulated by cytoplasmic phosphorylation

2003 ◽  
Vol 163 (1) ◽  
pp. 83-95 ◽  
Author(s):  
Ming-Sum Lee ◽  
Shih-Chu Kao ◽  
Cynthia A. Lemere ◽  
Weiming Xia ◽  
Huang-Chun Tseng ◽  
...  
Keyword(s):  
Cortical Neurons ◽  
Pyramidal Neurons ◽  
Kinase Inhibitors ◽  
Senile Plaque ◽  
Amyloid Β ◽  
Amyloid Β Peptide ◽  
Hippocampal Pyramidal Neurons ◽  
App Processing ◽  
App Metabolism ◽  
Aβ Generation

Amyloid-β peptide (Aβ) aggregate in senile plaque is a key characteristic of Alzheimer's disease (AD). Here, we show that phosphorylation of amyloid precursor protein (APP) on threonine 668 (P-APP) may play a role in APP metabolism. In AD brains, P-APP accumulates in large vesicular structures in afflicted hippocampal pyramidal neurons that costain with antibodies against endosome markers and the β-secretase, BACE1. Western blot analysis reveals increased levels of T668-phosphorylated APP COOH-terminal fragments in hippocampal lysates from many AD but not control subjects. Importantly, P-APP cofractionates with endosome markers and BACE1 in an iodixanol gradient and displays extensive colocalization with BACE1 in rat primary cortical neurons. Furthermore, APP COOH-terminal fragments generated by BACE1 are preferentially phosphorylated on T668 verses those produced by α-secretase. The production of Aβ is significantly reduced when phosphorylation of T668 is either abolished by mutation or inhibited by T668 kinase inhibitors. Together, these results suggest that T668 phosphorylation may facilitate the BACE1 cleavage of APP to increase Aβ generation.

Two Mechanisms That Raise Free Intracellular Calcium in Rat Hippocampal Neurons During Hypoosmotic and Low NaCl Treatment

2000 ◽  
Vol 83 (1) ◽  
pp. 81-89 ◽  
Author(s):  
Aren J. Borgdorff ◽  
George G. Somjen ◽  
Wytse J. Wadman
Keyword(s):  
Synaptic Transmission ◽  
Intracellular Calcium ◽  
Hippocampal Neurons ◽  
Pyramidal Neurons ◽  
Hippocampal Slices ◽  
Cell Swelling ◽  
Tissue Slices ◽  
Extracellular Medium ◽  
Calcium Activity ◽  
Hippocampal Pyramidal Neurons

Previous studies have shown that exposing hippocampal slices to low osmolarity (πo) or to low extracellular NaCl concentration ([NaCl]o) enhances synaptic transmission and also causes interstitial calcium ([Ca2+]o) to decrease. Reduction of [Ca2+]o suggests cellular uptake and could explain the potentiation of synaptic transmission. We measured intracellular calcium activity ([Ca2+]i) using fluorescent indicator dyes. In CA1 hippocampal pyramidal neurons in tissue slices, lowering πo by ∼70 mOsm caused “resting” [Ca2+]i as well as synaptically or directly stimulated transient increases of calcium activity (Δ[Ca2+]i) to transiently decrease and then to increase. In dissociated cells, lowering πo by ∼70 mOsm caused [Ca2+]i to almost double on average from 83 to 155 nM. The increase of [Ca2+]i was not significantly correlated with hypotonic cell swelling. Isoosmotic (mannitol- or sucrose-substituted) lowering of [NaCl]o, which did not cause cell swelling, also raised [Ca2+]i. Substituting NaCl with choline-Cl or Na-methyl-sulfate did not affect [Ca2+]i. In neurons bathed in calcium-free medium, lowering πo caused a milder increase of [Ca2+]i, which was correlated with cell swelling, but in the absence of external Ca2+, isotonic lowering of [NaCl]o triggered only a brief, transient response. We conclude that decrease of extracellular ionic strength (i.e., in both low πo and low [NaCl]o) causes a net influx of Ca2+ from the extracellular medium whereas cell swelling, or the increase in membrane tension, is a signal for the release of Ca2+ from intracellular stores.

P1-480: Amyloid β-peptide levels in laser capture microdissected CA1 pyramidal neurons of Alzheimer's brain

2008 ◽  
Vol 4 ◽  
pp. T360-T360
Author(s):  
Mikio Aoki ◽  
Inga Volkmann ◽  
Lars Tjernberg ◽  
Bengt Winblad ◽  
Nenad Bogdanovic
Keyword(s):  
Pyramidal Neurons ◽  
Amyloid Β ◽  
Amyloid Β Peptide ◽  
Ca1 Pyramidal Neurons ◽  
Laser Capture ◽  
Laser Capture Microdissected

scholarly journals Alzheimer’s amyloid-β peptide disturbs P2X7 receptor-mediated circadian oscillations of intracellular calcium

2016 ◽  
Vol 4 ◽  
pp. 360-368 ◽  
Author(s):  
Anna Wilkaniec ◽  
Karen Schmitt ◽  
Amandine Grimm ◽  
Joanna B. Strosznajder ◽  
Anne Eckert
Keyword(s):  
Intracellular Calcium ◽  
P2x7 Receptor ◽  
Amyloid Β ◽  
Amyloid Β Peptide

Intracellular Calcium Waves Transmit Synaptic Information to the Nucleus in Hippocampal Pyramidal Neurons

2007 ◽  
pp. 73-89 ◽  
Author(s):  
Mark F. Yeckel ◽  
Amanda A. Sleeper ◽  
John S. Fitzpatrick ◽  
Daniel N. Hertle ◽  
Anna M. Hagenston ◽  
...  
Keyword(s):  
Intracellular Calcium ◽  
Pyramidal Neurons ◽  
Calcium Waves ◽  
Hippocampal Pyramidal Neurons

scholarly journals Tetramethylpyrazine Derivative T-006 Ameliorates the Amyloid-β Plagues of Transgenic Alzhermer's Mice by Modulation of TLR4-mediated MyD88/NF-κB Signaling

2021 ◽  
Author(s):  
Haiyun Chen ◽  
Xiao Chang ◽  
Jiemei Zhou ◽  
Guiliang Zhang ◽  
Jiehong Cheng ◽  
...  
Keyword(s):  
Calcium Binding ◽  
Neuroprotective Effect ◽  
Amyloid Β ◽  
Trigger Factor ◽  
Amyloid Β Peptide ◽  
Protective Effects ◽  
Proinflammatory Mediators ◽  
Underlying Mechanisms ◽  
Related Proteins ◽  
Bv2 Microglial Cells

Abstract BackgroundMicroglial activation mediated neuroinflammation was considered as a vital trigger factor in the pathogenesis of Alzheimer’s disease (AD). T-006, a new tetramethylpyrazine derivative, has been recently found to alleviate cognitive deficits via inhibition of Tau expression and phosphorylation in AD transgenic mouse models. Here, we hypothesized that T-006 may ameliorate AD-like pathology by suppressing the neuroinflammation. MethodsAPP/PS1 transgenic AD mouse model was used here to evaluate the anti-inflammatory effect of T-006 and its underlying mechanisms, as well as its potential protective effects against lipopolysaccharide (LPS)-activated microglial-induced neurotoxicity.ResultsOur results indicated that T-006 significantly decreased the levels of total amyloid β peptide (Aβ) and glial fibrillary acidic protein (GFAP) as well as the ionized calcium binding adaptor molecule-1 (Ibα-1) expression in the APP/PS1 mice. Moreover, T-006 dramatically suppressed abnormal elevation of inflammatory mediators and reduced the levels of Toll-like receptor 4 (TLR4), myeloid differential protein-88 (MyD88) and NF-κB signaling related proteins in lipopolysaccharide (LPS)-induced BV2 microglial cells. We also found that TAK242, a TLR4 inhibitor could abolish the down-regulation of T-006 on LPS-induced proinflammatory mediators and reversed the downstream proteins expression containing MyD88 and NF-κB signaling. Importantly, T-006 prevented against neuroinflammation induced neurotoxicity by mitigating reactive oxygen species (ROS) overproduction and mitochondrial membrane potential (MMP) dissipation. Conclusions T-006 exerts neuroprotective effect in treating AD by suppressing the neuroinflammation through modulation of TLR4-mediated MyD88/NF-κB signaling pathways.

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