Neuronal damage and changes in the expression of muscarinic acetylcholine receptor subtypes in the neonatal rat cerebral cortical upon exposure to sparteine, a quinolizidine alkaloid.
Sparteine is a quinolizidine alkaloid (QA) produced by Lupine species that has generated much interest due to its anti-hypertensive, anti-pyretic, and anti-inflammatory properties. In the nervous system, sparteine has been shown to display anti-cholinergic and depressive activity, although how sparteine exerts its toxic effects in the brain remains unclear. We have addressed this issue by administering subcutaneous injections of sparteine (25 mg/kg of body weight) to rats on postnatal days 1 and 3, and then examining the expression of the muscarinic acetylcholine receptor (mAChR) subunits m1-m4 in the brains of the neonatal rats 14-60 days later. Administration of sparteine to neonatal rats caused neuronal damage in the cerebral motor cortex accompanied by transient changes in the expression of m1-m4 mAChR subunits as revealed by both RT-PCR and Western blotting. This effect could be prevented by pre-treatment with atropine (10 mg/kg) 1 h prior to the injection of sparteine, suggesting that the cytotoxic activity of sparteine is mediated through mAChRs.
Flores-Soto
M E
ME
Laboratory of Molecular and Cellular Neurobiology, Neurociences Division, Western Biomedical Research Center, Instituto Mexicano del Seguro Social, Guadalajara, Jalisco, Mexico.
Bañuelos-Pineda
J
J
Orozco-Suárez
S
S
Schliebs
R
R
Beas-Zárate
C
C
D000818:Animals; D000831:Animals, Newborn; D048430:Cell Shape; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D005260:Female; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D011247:Pregnancy; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D011976:Receptors, Muscarinic / Q000235:genetics / Q000378:metabolism*; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D013034:Sparteine / Q000008:administration & dosage / Q000633:toxicity*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D000099229:RE1-Silencing Transcription Factor
D021122:Protein Subunits; D011976:Receptors, Muscarinic; D012097:Repressor Proteins; D013034:Sparteine; D014157:Transcription Factors; D000099229:RE1-Silencing Transcription Factor