Clonidine increases caspase-3 mRNA level and DNA fragmentation in the developing rat brainstem.
The densities of alpha2-adrenergic receptors, labeled by 3H-clonidine or 3H-RX821002, reach a peak in the rat brainstem during the first week of its life. This enables the agonist of alpha2-adrenergic receptor clonidine, which is used as a component of anaesthetic solution in infants and children, to have specific effects in this structure of the developing brain. Clonidine was injected into the fetal brain (5 microg in 5 microl of saline) or subcutaneously to the pups (1, 10 microg in 50 microl of saline) 3 days before investigation. Clonidine increased the level of apoptotic enzyme caspase-3 mRNA expression, as measured by RT-PCR and enhanced the DNA fragmentation, as determined by gel electrophoresis, in the brainstem of the 21-day-old fetuses and 8-day-old rats. In the cortex of 8-day-old rat, the alpha2-adrenergic receptors are at a much lower level than the brainstem. Clonidine treatment had no evident effects on caspase-3 mRNA level and DNA fragmentation in the cortex of an 8-day-old rat. The data suggest that clonidine facilitates cell death in the developing brainstem. This drug effect provides a potential mechanism whereby clonidine during early life could induce long-lasting alterations in brain neurochemistry, autonomic functions and behavior.
Dygalo
Nikolai N
NN
Functional Neurogenomics Laboratory, Institute of Cytology and Genetics, Russian Academy of Science, Lavrentjev av. 10, Novosibirsk 630090, Russia. dygalo@bionet.nsc.ru
Bannova
Anita V
AV
Kalinina
Tatjana S
TS
Shishkina
Galina T
GT
D000316:Adrenergic alpha-Agonists / Q000378:metabolism / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000378:metabolism; D000375:Aging / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D001667:Binding, Competitive / Q000187:drug effects / Q000502:physiology; D001933:Brain Stem / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism*; D053148:Caspase 3; D020169:Caspases / Q000235:genetics*; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D003000:Clonidine / Q000378:metabolism / Q000494:pharmacology*; D053938:DNA Fragmentation / Q000187:drug effects* / Q000502:physiology; D005260:Female; D019329:Idazoxan / Q000031:analogs & derivatives / Q000378:metabolism; D008297:Male; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D018341:Receptors, Adrenergic, alpha-2 / Q000187:drug effects* / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D012333:RNA, Messenger; D018341:Receptors, Adrenergic, alpha-2; C058525:2-methoxyidazoxan; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases; D003000:Clonidine; D019329:Idazoxan