Please use this identifier to cite or link to this item: https://ahro.austin.org.au/austinjspui/handle/1/9271
Title: Differential modulatory effects of alpha- and beta-adrenoceptor agonists and antagonists on cortical immediate-early gene expression following focal cerebrocortical lesion-induced spreading depression.
Austin Authors: Shen, Pei-Juan;Gundlach, Andrew L
Affiliation: The University of Melbourne, Department of Medicine, Austin and Repatriation Medical Centre, Heidelberg, 3084, Victoria, Australia
Issue Date: 10-Nov-2000
Publication information: Brain Research. Molecular Brain Research; 83(1-2): 133-44
Abstract: Unilateral, focal cerebrocortical lesion (FCL) and associated spreading depression (SD) increase immediate-early gene (IEG) expression throughout the ipsilateral hemisphere. Noradrenergic transmission is involved in the regulation of basal- and stimulation-induced expression of IEGs in cerebral cortex; and is modulated by both injury and SD. The present study further investigated the association between the noradrenergic system and cortical adaptive responses, by examining basal and FCL(SD)-induced cortical IEG expression following acute treatment with alpha(1)-, alpha(2)- and beta(1/2)-adrenoceptor (AR) agonists or antagonists. Activation of alpha(1)-ARs by NVI-085, or beta-ARs by salbutamol, increased cortical NGFI-A, c-jun and c-fos mRNA levels, whereas inhibition of alpha(1)-ARs by prazosin, or beta-ARs by propranolol, had no marked effect. The alpha(2)-AR agonists, clonidine and UK14304 also had no effect on basal IEG levels, while blockade of alpha(2)-ARs by methoxyidazoxan significantly increased NGFI-A and c-fos expression, but decreased c-jun mRNA levels. This latter effect confirms the complex and differential nature of IEG regulation in brain. In FCL(SD) rats, all AR agonists generally produced a supra-additive (synergistic) effect on expression of the examined IEGs, compared with drug-treatment or FCL alone. Prazosin reduced FCL(SD)-induced elevations of c-jun and c-fos, but not NGFI-A, mRNA. Methoxyidazoxan enhanced NGFI-A and c-fos mRNA expression after FCL(SD), but reduced c-jun. Propranolol enhanced all lesion-induced IEG levels. These results confirm that alpha(1)- and beta-ARs normally mediate a stimulatory, and alpha(2)-ARs a net inhibitory, influence on cortical cell activity (reflected by NGFI-A, c-fos expression); and demonstrate that alterations in noradrenergic tone modulate the level of cellular activation during and after SD, which is primarily elicited by K(+)/glutamate via NMDA receptors and Ca(2+)-associated mechanisms. In turn, noradrenergic transmission and interactions with excitatory systems are likely to be important in responses to brain injury, including regulation of IEGs and their downstream target genes.
Gov't Doc #: 11072104
URI: https://ahro.austin.org.au/austinjspui/handle/1/9271
Journal: Brain Research. Molecular Brain Research
URL: https://pubmed.ncbi.nlm.nih.gov/11072104
Type: Journal Article
Subjects: Adrenergic alpha-Agonists.pharmacology
Adrenergic alpha-Antagonists.pharmacology
Adrenergic beta-Agonists.pharmacology
Adrenergic beta-Antagonists.pharmacology
Animals
Behavior, Animal.drug effects
Cerebral Cortex.drug effects.pathology.physiology
Cortical Spreading Depression.drug effects.physiology
DNA-Binding Proteins.genetics
Early Growth Response Protein 1
Gene Expression.drug effects
Genes, Immediate-Early.drug effects.genetics
Immediate-Early Proteins
In Situ Hybridization
Male
Proto-Oncogene Proteins c-fos.genetics
Proto-Oncogene Proteins c-jun.genetics
RNA, Messenger.analysis
Rats
Rats, Sprague-Dawley
Transcription Factors.genetics
Appears in Collections:Journal articles

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