scholarly journals Increased Amyloid-β Peptide-Induced Memory Deficits in Phospholipid Transfer Protein (PLTP) Gene Knockout Mice

2012 ◽  
Vol 38 (5) ◽  
pp. 817-825 ◽  
Author(s):  
Catherine Desrumaux ◽  
Amandine Pisoni ◽  
Johann Meunier ◽  
Valérie Deckert ◽  
Anne Athias ◽  
...  
Keyword(s):  
Knockout Mice ◽  
Gene Knockout ◽  
Amyloid Β ◽  
Memory Deficits ◽  
Amyloid Β Peptide ◽  
Phospholipid Transfer Protein ◽  
Transfer Protein ◽  
Phospholipid Transfer ◽  
Gene Knockout Mice

scholarly journals Disruption of Phospholipid Transfer Protein–Mediated High-Density Lipoprotein Maturation Reduces Scavenger Receptor BI Deficiency–Driven Atherosclerosis Susceptibility Despite Unexpected Metabolic Complications

2020 ◽  
Vol 40 (3) ◽  
pp. 611-623 ◽  
Author(s):  
Menno Hoekstra ◽  
Ronald J. van der Sluis ◽  
Reeni B. Hildebrand ◽  
Bart Lammers ◽  
Ying Zhao ◽  
...  
Keyword(s):  
Glucose Tolerance ◽  
Knockout Mice ◽  
Scavenger Receptor ◽  
Density Lipoprotein ◽  
Phospholipid Transfer Protein ◽  
Double Knockout ◽  
Metabolic Complications ◽  
Scavenger Receptor Bi ◽  
Transfer Protein ◽  
Phospholipid Transfer

Objective: We tested the hypothesis that enlarged, dysfunctional HDL (high-density lipoprotein) particles contribute to the augmented atherosclerosis susceptibility associated with SR-BI (scavenger receptor BI) deficiency in mice. Approach and Results: We eliminated the ability of HDL particles to fully mature by targeting PLTP (phospholipid transfer protein) functionality. Particle size of the HDL population was almost fully normalized in male and female SR-BI×PLTP double knockout mice. In contrast, the plasma unesterified cholesterol to cholesteryl ester ratio remained elevated. The PLTP deficiency-induced reduction in HDL size in SR-BI knockout mice resulted in a normalized aortic tissue oxidative stress status on Western-type diet. Atherosclerosis susceptibility was—however—only partially reversed in double knockout mice, which can likely be attributed to the fact that they developed a metabolic syndrome-like phenotype characterized by obesity, hypertriglyceridemia, and a reduced glucose tolerance. Mechanistic studies in chow diet–fed mice revealed that the diminished glucose tolerance was probably secondary to the exaggerated postprandial triglyceride response. The absence of PLTP did not affect LPL (lipoprotein lipase)-mediated triglyceride lipolysis but rather modified the ability of VLDL (very low-density lipoprotein)/chylomicron remnants to be cleared from the circulation by the liver through receptors other than SR-BI. As a result, livers of double knockout mice only cleared 26% of the fractional dose of [ 14 C]cholesteryl oleate after intravenous VLDL-like particle injection. Conclusions: We have shown that disruption of PLTP-mediated HDL maturation reduces SR-BI deficiency-driven atherosclerosis susceptibility in mice despite the induction of proatherogenic metabolic complications in the double knockout mice.

3×Tg-AD Mice Overexpressing Phospholipid Transfer Protein Improves Cognition Through Decreasing Amyloid-β Production and Tau Hyperphosphorylation

2021 ◽  
pp. 1-15
Author(s):  
Wen-Zhi Wang ◽  
Ming-Wei Li ◽  
Ying Chen ◽  
Li-Yuan Liu ◽  
Yong Xu ◽  
...  
Keyword(s):  
Glycogen Synthase ◽  
Senile Plaques ◽  
Amyloid Β ◽  
Tau Phosphorylation ◽  
Phospholipid Transfer Protein ◽  
Lipid Transfer ◽  
Neuroprotective Effects ◽  
Transfer Protein ◽  
Phospholipid Transfer ◽  
Exact Effect

Background: Phospholipid transfer protein (PLTP) belongs to the lipid transfer glycoprotein family. Studies have shown that it is closely related to Alzheimer’s disease (AD); however, the exact effect and mechanism remain unknown. Objective: To observe the effect of PLTP overexpression on behavioral dysfunction and the related mechanisms in APP/PS1/Tau triple transgenic (3×Tg-AD) mice. Methods: AAV-PLTP-EGFP was injected into the lateral ventricle to induce PLTP overexpression. The memory of 3×Tg-AD mice and wild type (WT) mice aged 10 months were assessed using Morris water maze (MWM) and shuttle-box passive avoidance test (PAT). Western blotting and ELISA assays were used to quantify the protein contents. Hematoxylin and eosin, Nissl, and immunochemistry staining were utilized in observing the pathological changes in the brain. Results: 3×Tg-AD mice displayed cognitive impairment in WMW and PAT, which was ameliorated by PLTP overexpression. The histopathological hallmarks of AD, senile plaques and neurofibrillary tangles, were observed in 3×Tg-AD mice and were improved by PLTP overexpression. Besides, the increase of amyloid-β42 (Aβ 42) and Aβ 40 were found in the cerebral cortex and hippocampus of 3×Tg-AD mice and reversed by PLTP overexpression through inhibiting APP and PS1. PLTP overexpression also reversed tau phosphorylation at the Ser404, Thr231 and Ser199 of the hippocampus in 3×Tg-AD mice. Furthermore, PLTP overexpression induced the glycogen synthase kinase 3β (GSK3β) inactivation via upregulating GSK3β (pSer9). Conclusion: These results suggest that PLTP overexpression has neuroprotective effects. These effects are possibly achieved through the inhibition of the Aβ production and tau phosphorylation, which is related to GSK3β inactivation.

Detrimental implication of B1 receptors in myocardial ischemia: evidence from pharmacological blockade and gene knockout mice

2002 ◽  
Vol 2 (6) ◽  
pp. 815-822 ◽  
Author(s):  
Caroline Lagneux ◽  
Michael Bader ◽  
João B. Pesquero ◽  
Pierre Demenge ◽  
Christophe Ribuot
Keyword(s):  
Myocardial Ischemia ◽  
Knockout Mice ◽  
Gene Knockout ◽  
B1 Receptors ◽  
Gene Knockout Mice ◽  
Pharmacological Blockade

Enhanced antinociceptive effects of morphine in histamine H2 receptor gene knockout mice

2006 ◽  
Vol 51 (3) ◽  
pp. 612-622 ◽  
Author(s):  
Jalal Izadi Mobarakeh ◽  
Kazuhiro Takahashi ◽  
Shinobu Sakurada ◽  
Atsuo Kuramasu ◽  
Kazuhiko Yanai
Keyword(s):  
Knockout Mice ◽  
Gene Knockout ◽  
Receptor Gene ◽  
Histamine H2 Receptor ◽  
H2 Receptor ◽  
Antinociceptive Effects ◽  
Gene Knockout Mice

scholarly journals Increased glycosphingolipid levels in serum and aortae of apolipoprotein E gene knockout mice

2002 ◽  
Vol 43 (2) ◽  
pp. 205-214 ◽  
Author(s):  
Brett Garner ◽  
David A. Priestman ◽  
Roland Stocker ◽  
David J. Harvey ◽  
Terry D. Butters ◽  
...  
Keyword(s):  
Apolipoprotein E ◽  
Knockout Mice ◽  
Gene Knockout ◽  
E Gene ◽  
Apolipoprotein E Gene ◽  
Gene Knockout Mice
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