Alzheimer-like phosphorylation of tau and neurofilament induced by cocaine in vivo.
OBJECTIVE
To explore the relationship between cocaine-induced cyclin-dependent kinase-5 (CDK5) overexpression or overactivation and Alzheimer-like hyperphosphorylation of cytoskeletal protein.


METHODS
Cocaine was injected (ip, 20 mg/kg/d) into rats and the phosphorylation of neuronal cytoskeletal proteins was measured by Western blotting.


RESULTS
The levels of phosphorylated tau at PHF-1 epitope and phosphorylated neurofilament determined by SMI31 were elevated in rat brain hippocampus, cortex, and caudatoputamen on d 8 and d 16 after the injection of cocaine, when compared with saline control rat at the same brain regions. On the other hand, the levels of tau non-phosphorylated at tau-1 site and non-phosphorylated neurofilament determined by SMI32 were decreased in same brain regions at the same time points examined. No significant difference of phosphorylated tau and neurofilament at those epitopes was seen on d 4. Although cocaine injection could induce significant hyperphosphorylation of neuronal cytoskeletal proteins, the overexpression of CDK5 and p35 was not detected.


CONCLUSIONS
Peritoneal injection of cocaine induces Alzheimer-like hyperphosphorylation of tau and neurofilament in rat brain, and the effect may be not relevant to an increase in overexpression or overactivation of CDK5.
Liu
Shi-Jie
SJ
Pathophysiology Department, Neuroscience Institute, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Fang
Zheng-Yu
ZY
Yang
Ying
Y
Deng
Heng-Mei
HM
Wang
Jian-Zhi
JZ
D000544:Alzheimer Disease / Q000378:metabolism; D000818:Animals; D001425:Bacterial Outer Membrane Proteins / Q000378:metabolism; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism; D003042:Cocaine / Q000494:pharmacology*; D051360:Cyclin-Dependent Kinase 5; D018844:Cyclin-Dependent Kinases / Q000378:metabolism; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D008074:Lipoproteins / Q000378:metabolism; D008297:Male; D016900:Neurofilament Proteins / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D010770:Phosphotransferases; D051381:Rats; D017207:Rats, Sprague-Dawley; D016875:tau Proteins / Q000378:metabolism*
D001425:Bacterial Outer Membrane Proteins; C492235:Cdk5r1 protein, rat; D018765:Dopamine Uptake Inhibitors; D008074:Lipoproteins; D016900:Neurofilament Proteins; D016875:tau Proteins; D010770:Phosphotransferases; D051360:Cyclin-Dependent Kinase 5; C495907:Cdk5 protein, rat; D018844:Cyclin-Dependent Kinases; D003042:Cocaine