Electroconvulsive seizure restores neurogenesis and hippocampus-dependent fear memory after disruption by irradiation.
Ongoing neurogenesis in the adult hippocampus is thought to play a role in learning and memory processes, and in response to antidepressant treatments. Low doses of irradiation (IRR) produce a significant long-lasting inhibitory effect on hippocampal neurogenesis that correlates with long-lasting behavioral deficits. Here we report that electroconvulsive seizure (ECS), which robustly increases adult neurogenesis in naïve animals, also reverses the disruption of neurogenesis produced by IRR exposure. Moreover, we find that vascular endothelial growth factor (VEGF) is an essential mediator of this effect. Expression of VEGF in the granule cell layer (GCL) of the hippocampus is decreased by IRR, and ECS administration reverses this deficit in VEGF. There is a corresponding alteration in the number of endothelial cells, which express VEGF, in the hippocampal GCL following IRR and ECS. We also find that blockade of VEGF signaling attenuates ECS-induced proliferation, and VEGF infusion partially restores proliferation in irradiated animals. To examine the functional consequences of IRR and ECS on neurogenesis, hippocampus-dependent contextual fear conditioning was assessed. We found that following disruption by IRR, ECS restores contextual learning to baseline levels at time points consistent with its effects on neurogenesis. These findings demonstrate that ECS, in part via induction of VEGF, can reverse long-term neurogenesis deficits resulting from IRR, and that these effects have functional consequences on hippocampus-dependent fear memory.
Warner-Schmidt
Jennifer L
JL
Laboratory of Molecular Psychiatry, Departments of Psychiatry and Pharmacology, Yale University School of Medicine, New Haven, CT, USA.
Madsen
Torsten M
TM
Duman
Ronald S
RS
D000818:Animals; D002454:Cell Differentiation / Q000502:physiology / Q000528:radiation effects*; D004597:Electroshock / Q000379:methods; D005239:Fear / Q000502:physiology / Q000528:radiation effects*; D005720:Gamma Rays; D006624:Hippocampus / Q000166:cytology* / Q000502:physiology / Q000528:radiation effects*; D008297:Male; D008568:Memory / Q000502:physiology / Q000528:radiation effects*; D009474:Neurons / Q000166:cytology / Q000528:radiation effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis / Q000502:physiology
D042461:Vascular Endothelial Growth Factor A