Regulation of activity-regulated cytoskeleton protein (Arc) mRNA after acute and chronic electroconvulsive stimulation in the rat.
The temporal profile of Arc gene expression after acute and chronic electroconvulsive stimulations (ECS) was studied using semi-quantitative in situ hybridisation in the rat cortex. A single ECS strongly and temporarily increased Arc mRNA levels in dentate granular cells with maximal induction seen up to 4 h after the stimulus, but returned to baseline at 24 h. A single ECS also increased expression of Arc mRNA in the CA1 and the parietal cortex, but the expression peaked within 1 h and returned to baseline levels within 2 h. Repeated or chronic ECS is a model of electroconvulsive therapy and it would be predicted that gene products involved in antidepressant effects accumulate after repeated ECS. However, repeated ECS reduced Arc gene expression in the CA1 24 h after the last stimulus. These results indicate that Arc is an immediate early gene product regulated by an acute excitatory stimulus, but not accumulated by long term repetitive ECS and therefore not a molecular biomarker for antidepressant properties. More likely, Arc is likely a molecular link to the decline in memory consolidation seen in depressive patients subjected to electroconvulsive therapy.
Larsen
M H
MH
Department of Functional Neuroanatomy and Biomarkers, Neurosearch A/S, Pederstrupvej 93, 2750 Ballerup, Denmark.
Olesen
M
M
Woldbye
D P D
DP
Hay-Schmidt
A
A
Hansen
H H
HH
Rønn
L C B
LC
Mikkelsen
J D
JD
D000818:Animals; D002540:Cerebral Cortex / Q000378:metabolism*; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism*; D003866:Depressive Disorder / Q000378:metabolism / Q000628:therapy; D004195:Disease Models, Animal; D004565:Electroconvulsive Therapy; D004597:Electroshock; D005786:Gene Expression Regulation / Q000502:physiology; D006624:Hippocampus / Q000378:metabolism; D008297:Male; D008568:Memory / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D010296:Parietal Lobe / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
D003598:Cytoskeletal Proteins; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; C092069:activity regulated cytoskeletal-associated protein