The phosphodiesterase 5 inhibitor, KJH-1002, reverses a mouse model of amnesia by activating a cGMP/cAMP response element binding protein pathway and decreasing oxidative damage

British Journal of Pharmacology
Lijun ZhangHyun Ok Yang

Abstract

Inhibition of PDE5 improves synaptic plasticity and memory via enhancing cGMP expression, thus activating the cGMP/cAMP response element binding protein (CREB) signalling pathway. This study investigated the effects of a PDE5 inhibitor on scopolamine-induced cognitive dysfunction, using memory-related behavioural tests and biochemical assays. In mice were pretreated with PDE5 inhibitor, amnesia was induced by scopolamine. The learning and memory abilities of mice were tested using the Morris water maze test, the Y-maze test, the passive avoidance test and the novel object recognition test in sequence. Expression of memory-related bio-molecules and oxidative stress parameters in brain tissue were measured using Western blot and spectrophotometry respectively. KJH-1002, a novel and potent inhibitor of PDE5 (IC50 0.059 ± 0.04 nmol·L-1 ), was synthesized. In the behavioural tests, it markedly improved the memory performance impaired by scopolamine, indicating a restoration of cognitive function in the mice. Moreover, KJH-1002 increased cGMP levels in the cortex and the scopolamine-reduced expression of phosphorylated CREB, Levels of ERK 1/2, Akt and brain-derived neurotrophic factor in the cortex and hippocampus were restored by KJ...Continue Reading

References

Jan 1, 1990·Methods in Enzymology·H Esterbauer, K H Cheeseman
Jan 19, 1971·Biochemistry·W J Thompson, M M Appleman
May 1, 1984·Journal of Neuroscience Methods·R Morris
Jan 1, 1997·Free Radical Biology & Medicine·W R Markesbery
Dec 14, 1999·European Journal of Pharmacology·C BejarM Weinstock
Aug 25, 2001·Annual Review of Neuroscience·E J Huang, L F Reichardt
May 1, 1959·Archives of Biochemistry and Biophysics·G L ELLMAN
Jul 1, 1961·Biochemical Pharmacology·G L ELLMANR M FEATHER-STONE
Nov 19, 2003·The Journal of Comparative Neurology·Wilma C G Van StaverenJan De Vente
Aug 18, 2004·Neurochemistry International·Jos PrickaertsArjan Blokland
Sep 21, 2007·Nature Reviews. Neuroscience·Vittorio CalabreseAnna Maria Giuffrida Stella
Aug 5, 2008·Neuropharmacology·F Josef van der StaayMartin Hendrix
Apr 18, 2009·Cell Adhesion & Migration·Alejandro Gella, Nuria Durany
Jun 26, 2009·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Daniela PuzzoOttavio Arancio
Apr 16, 2010·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Kirk I EricksonArthur F Kramer
Apr 17, 2010·Neuropharmacology·David J BondaMark A Smith
Apr 20, 2010·Neuroscience and Biobehavioral Reviews·Inge Klinkenberg, Arjan Blokland
May 8, 2010·Neurobiology of Aging·Beverly M FrancisHoward T J Mount
Jul 24, 2010·British Journal of Pharmacology·Carol KilkennyUNKNOWN NC3Rs Reporting Guidelines Working Group
Jun 2, 2011·British Journal of Pharmacology·M Cuadrado-TejedorA García-Osta
Feb 14, 2012·The Journal of Pharmacology and Experimental Therapeutics·Robin J KleimanChristopher J Schmidt
Nov 23, 2012·ACS Chemical Neuroscience·Ana García-OstaRafael Franco
Jan 29, 2013·Phytomedicine : International Journal of Phytotherapy and Phytopharmacology·Monica HancianuLucian Hritcu
Jan 24, 2014·Journal of Agricultural and Food Chemistry·Sung-Woon HongDong-Hyun Kim
May 13, 2014·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Eva BollenJos Prickaerts
May 13, 2015·British Journal of Pharmacology·John C McGrath, Elliot Lilley
Mar 12, 2016·Journal of Alzheimer's Disease : JAD·Andrew F TeichOttavio Arancio
Jul 28, 2016·European Journal of Medicinal Chemistry·Akanksha Kulshreshtha, Poonam Piplani

❮ Previous
Next ❯

Citations

Feb 15, 2020·Journal of Affective Disorders·Eduardo Duarte-SilvaChristina Peixoto
Jul 17, 2020·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Abid BhatMeena Kishore Sakharkar

❮ Previous
Next ❯

Related Concepts

Related Feeds

Alzheimer's Disease: Animal Models

Alzheimer's disease is a neurodegenerative disease which can be studied using various experimental systems. This feed focuses on animal models used for Alzheimer's disease research.