scholarly journals The Broad Spectrum Mixed-Lineage Kinase 3 Inhibitor URMC-099 Prevents Acute Microgliosis and Cognitive Decline in a Mouse Model of Perioperative Neurocognitive Disorders

2019 ◽  
Author(s):  
Patrick Miller-Rhodes ◽  
Cuicui Kong ◽  
Gurpreet S. Baht ◽  
Ramona M. Rodriguiz ◽  
William C. Wetsel ◽  
...  
Keyword(s):  
Mouse Model ◽  
Cognitive Decline ◽  
Broad Spectrum ◽  
Neurocognitive Disorders ◽  
Mixed Lineage Kinase ◽  
Mixed Lineage Kinase 3

scholarly journals The broad spectrum mixed-lineage kinase 3 inhibitor URMC-099 prevents acute microgliosis and cognitive decline in a mouse model of perioperative neurocognitive disorders

2019 ◽  
Author(s):  
Patrick Miller-Rhodes ◽  
Cuicui Kong ◽  
Gurpreet S. Baht ◽  
Ramona M. Rodriguiz ◽  
William C. Wetsel ◽  
...  
Keyword(s):  
Broad Spectrum ◽  
Orthopedic Surgery ◽  
Therapeutic Option ◽  
Postoperative Cognitive Dysfunction ◽  
Light Sheet ◽  
Neurocognitive Disorders ◽  
Mixed Lineage Kinase ◽  
Light Sheet Microscopy ◽  
Mixed Lineage Kinase 3 ◽  
Induced Changes

AbstractPerioperative neurocognitive disorders (PND), including delirium and postoperative cognitive dysfunction, are serious complications that afflict up to 50% of surgical patients and for which there are no disease-modifying therapeutic options. Here, we test whether prophylactic treatment with the broad spectrum mixed-lineage kinase 3 inhibitor URMC-099 prevents surgery-induced neuroinflammation and cognitive impairment in a translational model of orthopedic surgery-induced PND. We used a combination of two-photon scanning laser microscopy and CLARITY with light-sheet microscopy to define surgery-induced changes in microglial dynamics and morphology. Orthopedic surgery induced widespread microglial activation in the hippocampus and cortex that accompanied impairments in episodic memory. URMC-099 prophylaxis prevented these neuropathological sequelae without impacting bone fracture healing. Together, these findings provide compelling evidence for the advancement of URMC-099 as a therapeutic option for PND.

scholarly journals 24(S)-Saringosterol Prevents Cognitive Decline in a Mouse Model for Alzheimer’s Disease

Marine Drugs ◽  
2021 ◽  
Vol 19 (4) ◽  
pp. 190
Author(s):  
Nikita Martens ◽  
Melissa Schepers ◽  
Na Zhan ◽  
Frank Leijten ◽  
Gardi Voortman ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Model ◽  
Cognitive Decline ◽  
Inflammatory Marker ◽  
Amyloid Β ◽  
Liver Fat ◽  
Gas Chromatography Mass Spectrometry ◽  
Memory Decline ◽  
Plaque Load

We recently found that dietary supplementation with the seaweed Sargassum fusiforme, containing the preferential LXRβ-agonist 24(S)-saringosterol, prevented memory decline and reduced amyloid-β (Aβ) deposition in an Alzheimer’s disease (AD) mouse model without inducing hepatic steatosis. Here, we examined the effects of 24(S)-saringosterol as a food additive on cognition and neuropathology in AD mice. Six-month-old male APPswePS1ΔE9 mice and wildtype C57BL/6J littermates received 24(S)-saringosterol (0.5 mg/25 g body weight/day) (APPswePS1ΔE9 n = 20; C57BL/6J n = 19) or vehicle (APPswePS1ΔE9 n = 17; C57BL/6J n = 19) for 10 weeks. Cognition was assessed using object recognition and object location tasks. Sterols were analyzed by gas chromatography/mass spectrometry, Aβ and inflammatory markers by immunohistochemistry, and gene expression by quantitative real-time PCR. Hepatic lipids were quantified after Oil-Red-O staining. Administration of 24(S)-saringosterol prevented cognitive decline in APPswePS1ΔE9 mice without affecting the Aβ plaque load. Moreover, 24(S)-saringosterol prevented the increase in the inflammatory marker Iba1 in the cortex of APPswePS1ΔE9 mice (p < 0.001). Furthermore, 24(S)-saringosterol did not affect the expression of lipid metabolism-related LXR-response genes in the hippocampus nor the hepatic neutral lipid content. Thus, administration of 24(S)-saringosterol prevented cognitive decline in APPswePS1ΔE9 mice independent of effects on Aβ load and without adverse effects on liver fat content. The anti-inflammatory effects of 24(S)-saringosterol may contribute to the prevention of cognitive decline.

scholarly journals Naphthalene Monoimide Derivative Ameliorates Amyloid Burden and Cognitive Decline in a Transgenic Mouse Model of Alzheimer's Disease

2021 ◽  
pp. 2000225
Author(s):  
Sourav Samanta ◽  
Kolla Rajasekhar ◽  
Madhu Ramesh ◽  
Natarajan Arul Murugan ◽  
Shadab Alam ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Model ◽  
Cognitive Decline ◽  
Transgenic Mouse ◽  
Transgenic Mouse Model ◽  
Amyloid Burden ◽  
Model Of Alzheimer’S Disease

scholarly journals Mixed Lineage Kinase 3 Mediates the Induction of CXCL10 by a STAT1-Dependent Mechanism During Hepatocyte Lipotoxicity

2017 ◽  
Vol 118 (10) ◽  
pp. 3249-3259 ◽  
Author(s):  
Kyoko Tomita ◽  
Ayano Kabashima ◽  
Brittany L. Freeman ◽  
Steven F. Bronk ◽  
Petra Hirsova ◽  
...  
Keyword(s):  
Mixed Lineage Kinase ◽  
Mixed Lineage Kinase 3 ◽  
Dependent Mechanism

scholarly journals Mixed lineage kinase 3 deficient mice are protected against the high fat high carbohydrate diet-induced steatohepatitis

2013 ◽  
Vol 34 (3) ◽  
pp. 427-437 ◽  
Author(s):  
Samar H. Ibrahim ◽  
Gregory J. Gores ◽  
Petra Hirsova ◽  
Michelle Kirby ◽  
Lili Miles ◽  
...  
Keyword(s):  
High Carbohydrate Diet ◽  
High Fat ◽  
Carbohydrate Diet ◽  
Mixed Lineage Kinase ◽  
High Carbohydrate ◽  
Mixed Lineage Kinase 3 ◽  
Deficient Mice

Mixed Lineage Kinase 3 phosphorylates prolyl-isomerase PIN1 and potentiates GLI1 signaling in pancreatic cancer development

2021 ◽  
Author(s):  
Navin Viswakarma ◽  
Gautam Sondarva ◽  
Daniel R. Principe ◽  
Rakesh Sathish Nair ◽  
Sandeep Kumar ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Development ◽  
Prolyl Isomerase ◽  
Mixed Lineage Kinase ◽  
Mixed Lineage Kinase 3

scholarly journals Intranasal rapamycin ameliorates Alzheimer-like cognitive decline in a mouse model of Down syndrome

2018 ◽  
Vol 7 (1) ◽  
Author(s):  
Antonella Tramutola ◽  
Chiara Lanzillotta ◽  
Eugenio Barone ◽  
Andrea Arena ◽  
Ilaria Zuliani ◽  
...  
Keyword(s):  
Down Syndrome ◽  
Mouse Model ◽  
Cognitive Decline
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