Electroconvulsive seizures stimulate glial proliferation and reduce expression of Sprouty2 within the prefrontal cortex of rats.
BACKGROUND
Reductions in cell number are found within the medial prefrontal cortex (PFC) in major depression and bipolar disorder, conditions for which electroconvulsive therapy (ECT) is a highly effective treatment. We investigated whether electroconvulsive seizure (ECS) in rats stimulates cellular proliferation in the PFC immediately and four weeks after the treatments. In parallel, we examined if ECS also alters the expression of Sprouty2 (SPRY2), an inhibitor of cell proliferation.


METHODS
Sprague-Dawley rats received 10 days of ECS treatments and bromodeoxyuridine (BrdU) injections. After a four week survival period, we estimated the density and number of BrdU-, proliferating cell nuclear antigen (PCNA)-, and SPRY2-immunoreactive cells in the medial (infralimbic) PFC (ILPFC). We also determined the percentage of BrdU-labeled cells that were immunoreactive for markers specific to oligodendrocytes, astrocytes, endothelial cells and neurons.


RESULTS
ECS dramatically enhanced the proliferation of new cells in the infralimbic PFC, and this effect persisted four weeks following the treatments. The percentage of new cells expressing oligodendrocyte precursor cell markers increased slightly following ECS. In contrast, ECS dramatically reduced the number of cells expressing SPRY2.


CONCLUSIONS
ECS stimulates long-lasting increases in glial proliferation within the ILPFC. ECS also decreases SPRY2 expression in the same region, an effect that might contribute to increased glial proliferation.
Ongür
Dost
D
Department of Psychiatry, Harvard Medical School and McLean Hospital, Belmont, Massachusetts 02478, USA. dongur@partners.org
Pohlman
Jessica
J
Dow
Antonia L
AL
Eisch
Amelia J
AJ
Edwin
Francis
F
Heckers
Stephan
S
Cohen
Bruce M
BM
Patel
Tarun B
TB
Carlezon
William A
WA
D000704:Analysis of Variance; D000818:Animals; D000941:Antigens / Q000378:metabolism; D001973:Bromodeoxyuridine / Q000378:metabolism; D002452:Cell Count / Q000379:methods; D049109:Cell Proliferation / Q000528:radiation effects*; D004597:Electroshock; D005786:Gene Expression Regulation / Q000502:physiology / Q000528:radiation effects; D008297:Male; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009457:Neuroglia / Q000473:pathology*; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D017397:Prefrontal Cortex / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology / Q000528:radiation effects; D011509:Proteoglycans / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012640:Seizures / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D000099216:Chondroitin Sulfate Proteoglycan 4
D000941:Antigens; D001973:Bromodeoxyuridine; D009419:Nerve Tissue Proteins; D011509:Proteoglycans; D000099216:Chondroitin Sulfate Proteoglycan 4; C404992:Spry2 protein, rat