Rapid and long-term induction of effector immediate early genes (BDNF, Neuritin and Arc) in peri-infarct cortex and dentate gyrus after ischemic injury in rat brain.
The genomic response following brain ischemia is very complex and involves activation of both protective and detrimental signaling pathways. Immediate early genes (IEGs) represent the first wave of gene expression following ischemia and are induced in extensive regions of the ischemic brain including cerebral cortex and hippocampus. Brain-derived neurotrophic factor (BDNF), Neuritin and Activity-regulated cytoskeleton-associated protein (Arc) belong to a subgroup of immediate early genes implicated in synaptic plasticity known as effector immediate early genes. Here, we investigated the spatial and temporal activation pattern for these genes during the first 24 h of reperfusion following 2-h occlusion of the middle cerebral artery. Neuritin showed a persistent activation in frontal-cingulate cortex while Arc displayed a biphasic response. Also, in dentate gyrus, activation was observed at 0-6 h of reperfusion for Neuritin and 0-12 h of reperfusion for Arc while BDNF was induced 0-9 h of reperfusion. Our study demonstrates a rapid and long-term activation of effector immediate early genes in distinct brain areas following ischemic injury in rat. Effector gene activation may be part of long-term synaptic responses of ischemic brain tissue.
Rickhag
Mattias
M
Laboratory for Experimental Brain Research, Wallenberg Neuroscience Center, University of Lund, BMC A13, 22184 Lund, Sweden. Mattias.Rickhag@med.lu.se
Teilum
Maria
M
Wieloch
Tadeusz
T
D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism*; D020520:Brain Infarction / Q000209:etiology / Q000473:pathology*; D002545:Brain Ischemia / Q000150:complications / Q000473:pathology; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism*; D002540:Cerebral Cortex / Q000378:metabolism*; D018891:Dentate Gyrus / Q000378:metabolism*; D058851:GPI-Linked Proteins; D005786:Gene Expression Regulation / Q000502:physiology; D017403:In Situ Hybridization / Q000379:methods; D008297:Male; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism*; D009479:Neuropeptides / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013997:Time Factors; D015533:Transcriptional Activation
D051017:Apoptosis Regulatory Proteins; D019208:Brain-Derived Neurotrophic Factor; D058851:GPI-Linked Proteins; D009124:Muscle Proteins; D009479:Neuropeptides; C491788:Nol3 protein, rat; C105161:Nrn1 protein, rat; D012333:RNA, Messenger