Bilateral injection of isoproterenol into hippocampus induces Alzheimer-like hyperphosphorylation of tau and spatial memory deficit in rat.
The abnormal hyperphosphorylation of tau protein is one of the hallmarks of Alzheimer disease and other tauopathies; as yet the exact role of various tau kinases in this pathology is not fully understood. Here, we show that injection of isoproterenol, an activator of cAMP-dependent kinase (PKA), into rat hippocampus bilaterally results in the activation of PKA, calcium/calmodulin-dependent kinase II and cyclin-dependent kinase-5, inhibition of protein phosphatase-2A, hyperphosphorylation of tau at several Alzheimer-like epitopes and a disturbance of spatial memory retention 48 h after the drug injection. These findings suggest the involvement of PKA and PKA-mediated signaling pathway in the Alzheimer-like tau hyperphosphorylation and memory impairment.
Sun
Li
L
Department of Pathophysiology, Institute of Neuroscience, Tongji Medical College, Huazhong University of Science and Technology, 13 Hang Kong Road, Wuhan 430030, PR China.
Wang
XiaoChuang
X
Liu
Shengyuan
S
Wang
Quan
Q
Wang
JianZhi
J
Bennecib
Malika
M
Gong
Cheng-Xin
CX
Sengupta
Amitabha
A
Grundke-Iqbal
Inge
I
Iqbal
Khalid
K
D000544:Alzheimer Disease / Q000201:enzymology; D000818:Animals; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000502:physiology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism* / Q000502:physiology; D051360:Cyclin-Dependent Kinase 5; D018844:Cyclin-Dependent Kinases / Q000378:metabolism / Q000502:physiology; D006624:Hippocampus / Q000187:drug effects / Q000201:enzymology*; D007267:Injections; D007545:Isoproterenol / Q000008:administration & dosage; D008569:Memory Disorders / Q000139:chemically induced / Q000201:enzymology*; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D013037:Spatial Behavior / Q000187:drug effects; D016875:tau Proteins / Q000032:analysis / Q000378:metabolism*
D016875:tau Proteins; D051360:Cyclin-Dependent Kinase 5; D017868:Cyclic AMP-Dependent Protein Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; C495907:Cdk5 protein, rat; D018844:Cyclin-Dependent Kinases; D007545:Isoproterenol