Melanocortin-4 receptor messenger RNA expression is up-regulated in the non-damaged striatum following unilateral hypoxic-ischaemic brain injury.
Melanocortin peptides (alpha-melanocyte-stimulating hormone, adrenocorticotropin and fragments thereof) have been shown to have numerous effects on the central nervous system, including recovery from nerve injury and retention of learned behaviour, but the mechanism of action of these peptides is unknown. A family of five melanocortin receptors have recently been discovered, two of which (melanocortin-3 and melanocortin-4 receptors) have been mapped in the rat brain. We have tested the hypothesis that the expression of one or more of the messenger RNAs for three melanocortin receptors (melanocortin-3, melanocortin-4 and melanocortin-5 receptors) would be altered in rat brain following unilateral transient hypoxic-ischaemic brain injury. In this study, using in situ hybridization, we show that melanocortin-4 receptor messenger RNA was up-regulated in the striatum in the non-damaged hemisphere within 24 h after severe hypoxic-ischaemic injury compared with control brains (P<0.05). In a small group of animals, this induction was not blocked by treatment with the anticonvulsant, carbamazepine. Expression of melanocortin-3 receptor messenger RNA in the brain was not altered in this hypoxic-ischaemic injury model and melanocortin-5 receptor messenger RNA was not detected in either control or hypoxic-ischaemic injured rat brains. We hypothesize that the up-regulation of melanocortin-4 receptor messenger RNA expression in the contralateral striatum may be involved in transfer of function to the uninjured hemisphere following unilateral brain injury.
Department of Paediatrics, University of Auckland, New Zealand.
K G
KG
Mountjoy
J
J
Guan
C J
CJ
Elia
E S
ES
Sirimanne
C E
CE
Williams
D000818:Animals; D002545:Brain Ischemia / Q000378:metabolism*; D003342:Corpus Striatum / Q000737:chemistry / Q000166:cytology*; D007839:Functional Laterality; D015870:Gene Expression / Q000502:physiology; D006624:Hippocampus / Q000737:chemistry / Q000166:cytology; D002534:Hypoxia, Brain / Q000378:metabolism*; D009474:Neurons / Q000737:chemistry* / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D044105:Receptor, Melanocortin, Type 4; D018043:Receptors, Corticotropin / Q000235:genetics / Q000378:metabolism; D044101:Receptors, Melanocortin; D018000:Receptors, Peptide / Q000235:genetics* / Q000378:metabolism; D015854:Up-Regulation / Q000502:physiology
D012333:RNA, Messenger; D044105:Receptor, Melanocortin, Type 4; D018043:Receptors, Corticotropin; D044101:Receptors, Melanocortin; D018000:Receptors, Peptide; C086971:melanocortin 5 receptor