c-fos antisense reduces expression of Krox 24 in rat caudate and neocortex.
1. The aim of this study was to investigate the neurochemical effects and measure the anatomical spread of infusion of c-fos antisense (AS) DNA into the striatum. 2. Rats were anesthetized and infused in opposing striata with c-fos AS and c-fos sense (S) DNA. Ten hours later they were injected with apomorphine (2 mg/kg, i.p.) and 20 min later they were overdosed with sodium pentobarbital and their brains either perfused or frozen. Vibratome-cut sections were immunostained for the detection of c-fos, JunB, Krox 24, somatostatin, substance P, dynorphin, tyrosine hydroxylase, and enkephalin. Cryostat-cut sections from the caudate were immunostained for the detection of c-fos, JunB, and Krox 24, as well as in situ hybridization for proenkephalin mRNA. Sections from the globus pallidus were used for the autoradiographic localization of D2 dopamine and A2a adenosine receptors. Sections from the substantia nigra were used for the autoradiographic localization of D1 dopamine and cannabinoid receptors. A second group of rats were injected in opposing striata with biotin-labeled c-fos AS DNA and c-fos S DNA. Ten hours later they were challenged with apomorphine (2 mg/kg, i.p.) and 20 min later brains were either perfused or frozen. Sections from these brains were cut throughout the rostral-caudal extent of the forebrain and the biotin labeled AS DNA was localized. 3. Krox 24 was expressed at high levels on the sense side of the brain in the striatum and overlying neocortex. However, on the AS-injected side there was a reduction in Krox 24 expression in striatum and overlying cortex. The biotin-labeled AS studies confirmed that the striatal infusion spread throughout the dorsal striatum as well as the overlying neocortex. We did not detect any changes in neurotransmitter receptors, neuropeptides, or tyrosine hydroxylase in AS/S-injected rat brains. 4. These results demonstrate that c-fos AS reduces Krox 24 expression in striatal and neocortical neurons but does not change the expression of a number of other proteins involved in basal ganglia function. Whether this effect is due to nonspecific actions of c-fos AS or to its effects on a component of the transduction pathway responsible for basal Krox 24 expression (NMDA receptors?) is unknown.
Dragunow
M
M
Department of Pharmacology and Clinical Pharmacology, School of Medicine, University of Auckland, New Zealand.
Tse
C
C
Glass
M
M
Lawlor
P
P
D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D001479:Basal Ganglia / Q000187:drug effects / Q000378:metabolism; D001483:Base Sequence; D002421:Caudate Nucleus / Q000187:drug effects* / Q000378:metabolism; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism; D004247:DNA / Q000494:pharmacology; D016373:DNA, Antisense / Q000494:pharmacology*; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics*; D004298:Dopamine / Q000378:metabolism; D018491:Dopamine Agonists / Q000494:pharmacology; D051766:Early Growth Response Protein 1; D005786:Gene Expression Regulation / Q000187:drug effects*; D016762:Genes, fos; D016758:Genes, jun; D017874:Immediate-Early Proteins; D008297:Male; D008969:Molecular Sequence Data; D009043:Motor Activity / Q000187:drug effects; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000235:genetics*; D009479:Neuropeptides / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D043882:Receptors, Cannabinoid; D011954:Receptors, Dopamine / Q000096:biosynthesis / Q000145:classification / Q000235:genetics; D011955:Receptors, Drug / Q000096:biosynthesis / Q000235:genetics; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics*; D014158:Transcription, Genetic; D014446:Tyrosine 3-Monooxygenase / Q000096:biosynthesis / Q000235:genetics
D016373:DNA, Antisense; D004268:DNA-Binding Proteins; D018491:Dopamine Agonists; D051766:Early Growth Response Protein 1; C486110:Egr1 protein, rat; D017874:Immediate-Early Proteins; D009419:Nerve Tissue Proteins; D009479:Neuropeptides; D043882:Receptors, Cannabinoid; D011954:Receptors, Dopamine; D011955:Receptors, Drug; D014157:Transcription Factors; D004247:DNA; D014446:Tyrosine 3-Monooxygenase; D001058:Apomorphine; D004298:Dopamine