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Title: Differential spatiotemporal alterations in adrenoceptor mRNAs and binding sites in cerebral cortex following spreading depression: selective and prolonged up-regulation of alpha1B-adrenoceptors.
Austin Authors: Shen, Pei-Juan;Gundlach, Andrew L
Affiliation: The University of Melbourne, Department of Medicine, Austin and Repatriation Medical Centre, Heidelberg, Victoria, 3084, Australia
Issue Date: 1-Dec-1998
Publication information: Experimental Neurology; 154(2): 612-27
Abstract: Noradrenaline, an important transmitter in the CNS, is involved in cerebral plasticity and functional recovery after injury. Experimental brain injury, including KCl application onto the brain surface, induces a slow-moving cortical depolarization/depression wave called cortical spreading depression (CSD). Interestingly, CSD does not produce neuronal damage but can protect cortical neurons against subsequent neurotoxic insults, although the mechanisms involved are unknown. This study examined the status of alpha- and beta-adrenoceptors (ARs) in cerebral cortex following CSD. Anesthetized rats had unilateral CSD induced by a 10-min topical application of KCl to the frontoparietal cortex and were killed at various times thereafter. Levels of alpha1-, alpha2-, beta1-, and beta2-AR mRNA and binding were examined using in situ hybridization histochemistry and radioligand autoradiography. Levels of alpha1b-AR mRNA in the affected neocortex were significantly increased by 20-40% at 1, 2, and 7 days (P </= 0.01) compared with contralateral levels, but were not significantly above control values at 2 and 4 weeks after CSD induction. Cortical alpha1B-AR binding sites were also increased by 45-65% 1 and 2 weeks (P </= 0.01) after CSD in a similar, but delayed, profile to alpha1b-AR mRNA. CSD rapidly increased beta1-AR mRNA by 45% at 1 h (P </= 0.01) and produced a delayed decrease of 25% in alpha2a-AR mRNA at 2 days and 1 week (P </= 0.05), but had no effect on corresponding levels of binding sites. In contrast, CSD had no effect on the remaining AR-subtype mRNAs or binding levels in neocortex under identical conditions. These results reveal a long-term up-regulation of alpha1B-ARs induced by an acute cortical stimulation/depression. Subtype-selective responses of ARs to CSD reflect an important differential regulation of expression of each receptor in vivo and suggest that alpha1B-ARs are particularly likely to be involved in cortical adaptive responses to physical injury at both local and distant locations.
Gov't Doc #: 9878196
DOI: 10.1006/exnr.1998.6915
Journal: Experimental neurology
Type: Journal Article
Subjects: Action Potentials.drug effects
Adrenergic alpha-Antagonists.metabolism.pharmacology
Binding, Competitive.physiology
Brain Chemistry.drug effects.physiology
Cerebral Cortex.chemistry.cytology.physiology
Cortical Spreading Depression.physiology
Gene Expression.physiology
In Situ Hybridization
Oligonucleotide Probes
Potassium Chloride.pharmacology
RNA, Messenger.analysis
Rats, Sprague-Dawley
Receptors, Adrenergic, alpha-1.genetics.metabolism
Time Factors
Tritium.diagnostic use
Appears in Collections:Journal articles

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