Chronic NMDA administration to rats increases brain pro-apoptotic factors while decreasing anti-Apoptotic factors and causes cell death.
BACKGROUND
Chronic N-Methyl-d-aspartate (NMDA) administration to rats is reported to increase arachidonic acid signaling and upregulate neuroinflammatory markers in rat brain. These changes may damage brain cells. In this study, we determined if chronic NMDA administration (25 mg/kg i.p., 21 days) to rats would alter expression of pro- and anti-apoptotic factors in frontal cortex, compared with vehicle control.


RESULTS
Using real time RT-PCR and Western blotting, chronic NMDA administration was shown to decrease mRNA and protein levels of anti-apoptotic markers Bcl-2 and BDNF, and of their transcription factor phospho-CREB in the cortex. Expression of pro-apoptotic Bax, Bad, and 14-3-3zeta was increased, as well as Fluoro-Jade B (FJB) staining, a marker of neuronal loss.


CONCLUSIONS
This alteration in the balance between pro- and anti-apoptotic factors by chronic NMDA receptor activation in this animal model may contribute to neuronal loss, and further suggests that the model can be used to examine multiple processes involved in excitotoxicity.
Kim
Hyung-Wook
HW
Brain Physiology and Metabolism Section, National Institute on Aging, National Institutes of Health, Bethesda, MD 20892, USA. kimhyung@mail.nih.gov
Chang
Yunyoung C
YC
Chen
Mei
M
Rapoport
Stanley I
SI
Rao
Jagadeesh S
JS
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D018690:Excitatory Amino Acid Agonists / Q000008:administration & dosage; D005625:Frontal Lobe / Q000187:drug effects / Q000378:metabolism*; D007274:Injections, Intraperitoneal; D008297:Male; D016202:N-Methylaspartate / Q000008:administration & dosage*; D010766:Phosphorylation / Q000187:drug effects; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013347:Subcellular Fractions
D019208:Brain-Derived Neurotrophic Factor; D017362:Cyclic AMP Response Element-Binding Protein; D018690:Excitatory Amino Acid Agonists; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D016202:N-Methylaspartate