Inhibition of glycogen synthase kinase 3β improves cognitive function in aged mice by upregulating claudin presences in cerebral endothelial cells

Acta Biochimica Et Biophysica Sinica
Tao LiangHao Fang

Abstract

Glycogen synthase kinase-3β (GSK-3β), a serine/threonine protein kinase, is widely distributed in mammalian brains. Since GSK-3β plays a vital role in the development of neurodegenerative disorders, the present study was designed to investigate the role of GSK-3β in the blood-brain barrier (BBB) permeability in aged mice. Morris water maze test was used to examine mouse cognitive function. BBB permeability was examined by the leakage of fluorescence signals of low-molecular weight dextran. GSK-3β inhibitor, 4-benzyl-2-methyl-1,2,4-thiadiazolidine-3,5-dione (TDZD-8), was administrated in aged mice and in cultured mouse brain microvascular endothelial cells (bEnd.3). Compared with young mice, aged mice had increased leftover signals of dextran in the hippocampus and a lower score in the maze test, suggesting that aged mice have abnormal leakage of BBB and cognitive dysfunction. The protein expression of Toll-like receptor 4 (TLR4) was increased, whereas the protein expressions of junction proteins (claudin1 and claudin5) were reduced in endothelial cells of BBB in aged mice. Phosphorylated level of serine 9, an inhibitory residue in GSK-3β protein, was decreased. TDZD-8 treatment downregulated TLR4 protein expression, upregulated...Continue Reading

References

Aug 23, 2001·Brain Research. Brain Research Reviews·R D'Hooge, P P De Deyn
Jul 23, 2003·Memory & Cognition·Klaus OberauerReinhold Kliegl
May 26, 2005·Pharmacological Reviews·Brian T Hawkins, Thomas P Davis
May 12, 2006·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Tobias EngelJosé J Lucas
Nov 6, 2007·Cellular Physiology and Biochemistry : International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology·Silke WalterKlaus Fassbender
Jul 30, 2010·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Xiaohua Li, Richard S Jope
Oct 1, 2011·The Journal of Pathology·Agnieszka KaczmarekDmitri V Krysko
Nov 17, 2011·Ageing Research Reviews·Giuliana KlencklenAndré Dufour
Jan 18, 2012·Neuroimmunomodulation·Michelle A EricksonWilliam A Banks
Jul 13, 2012·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·David Fernández-LópezZinaida S Vexler
Oct 25, 2012·Current Pharmaceutical Design·Khalid A HanafyLeo E Otterbein
Jun 19, 2014·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Oliver BrackoSusanne Wegener
Jan 23, 2015·Neuron·Axel MontagneBerislav V Zlokovic
Mar 17, 2015·European Journal of Pharmacology·Tien-Yao TsaiYuk-Man Leung
Mar 17, 2015·Neuroscience·R M BarrientosS F Maier
Jan 16, 2016·BioMed Research International·Xian ZhangJianhe Gan
Mar 21, 2016·Brain, Behavior, and Immunity·Aravinthan Varatharaj, Ian Galea
Mar 22, 2016·BMB Reports·Ryeojin Ko, Soo Young Lee
Mar 29, 2016·International Journal of Biological Sciences·Yixin LiYong Zhao
Sep 14, 2017·International Journal of Molecular Sciences·Yu Yamazaki, Takahisa Kanekiyo
Jan 4, 2018·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Allison M JohnsonAnuska V Andjelkovic
Feb 8, 2018·Acta Neuropathologica·Stefan LiebnerGabriela Constantin
Jun 7, 2018·Cell Metabolism·Mark P Mattson, Thiruma V Arumugam
Aug 22, 2018·Frontiers in Pharmacology·Xiaohong CenKui Cheng
Nov 1, 2018·American Journal of Physiology. Cell Physiology·Changjun YangEduardo Candelario-Jalil

❮ Previous
Next ❯

Related Concepts

Related Feeds

Blood Brain Barrier Regulation in Health & Disease

The blood brain barrier is essential in regulating the movement of molecules and substances in and out of the brain. Disruption to the blood brain barrier and changes in permeability allow pathogens and inflammatory molecules to cross the barrier and may play a part in the pathogenesis of neurodegenerative disorders. Here is the latest research in this field.

Blood Brain Barrier Chips

The blood brain barrier (BBB) is comprised of endothelial cells that regulate the influx and outflux of plasma concentrations. Lab-on-a-chip devices allow scientists to model diseases and mechanisms such as the passage of therapeutic antibodies across the BBB. Discover the latest research on BBB chips here.

Blood Brain Barrier

The blood brain barrier is a border that separates blood from cerebrospinal fluid. Discover the latest search on this highly selective semipermeable membrane here.

Brain Aging

Here is the latest research on intrinsic and extrinsic factors, as well as pathways and mechanisms that underlie aging in the central nervous system.