Electroconvulsive seizure increases adult hippocampal angiogenesis in rats.
Electroconvulsive seizure has a proven therapeutic application in the treatment of severe depression and treatment-resistant depression. Despite the efficacy of electroconvulsive seizure as a non-chemical antidepressant treatment, the mechanism of action is unclear. Elevation in hippocampal trophic factor expression and concomitant cellular proliferation are thought to play a role in its action. We examined whether the reported induction of angiogenic factors and endothelial cell proliferation leads to an increase in vascular density. Two hippocampal regions, the dentate gyrus and the stratum lacunosum moleculare (SLM), were examined employing a combination of vascular density quantification, angiogenic gene expression analysis and immunohistochemistry. A 6% increase in vascular density was observed in the dentate gyrus but this did not achieve statistical significance. The SLM of the hippocampus exhibited a robust 20-30% increase in vascular density and was accompanied by an increase in expression of inhibitor of differentiation-3. There was also an induction of the angiogenesis markers alphaVbeta3 integrin and Del1. Increases in the vascular density of the SLM could be in response to enhanced metabolic activity in this region. This is supported by the induction of glutamine synthetase and the glutamate transporter GLT1.
Newton
Samuel S
SS
Division of Molecular Psychiatry, Abraham Ribicoff Research Facilities, Connecticut Mental Health Center, Yale University School of Medicine, New Haven, CT, USA. Samuel.Sathyanesan@yale.edu
Girgenti
Matthew J
MJ
Collier
Emily F
EF
Duman
Ronald S
RS
D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001808:Blood Vessels / Q000378:metabolism*; D002135:Calcium-Binding Proteins; D002352:Carrier Proteins / Q000378:metabolism; D015815:Cell Adhesion Molecules; D018891:Dentate Gyrus / Q000098:blood supply / Q000378:metabolism; D003866:Depressive Disorder / Q000503:physiopathology / Q000628:therapy*; D004565:Electroconvulsive Therapy; D027342:Excitatory Amino Acid Transporter 2 / Q000378:metabolism; D005974:Glutamate-Ammonia Ligase / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism; D006624:Hippocampus / Q000098:blood supply* / Q000378:metabolism*; D051796:Inhibitor of Differentiation Proteins / Q000378:metabolism; D039302:Integrin alphaVbeta3 / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins; D008297:Male; D018919:Neovascularization, Physiologic / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015854:Up-Regulation / Q000502:physiology
D015415:Biomarkers; D002135:Calcium-Binding Proteins; D002352:Carrier Proteins; D015815:Cell Adhesion Molecules; C491706:Edil3 protein, mouse; D027342:Excitatory Amino Acid Transporter 2; D051796:Inhibitor of Differentiation Proteins; D039302:Integrin alphaVbeta3; D036341:Intercellular Signaling Peptides and Proteins; D018698:Glutamic Acid; C081173:glutamine synthetase I; D005974:Glutamate-Ammonia Ligase