Ongür Dost, Pohlman Jessica, Dow Antonia L, Eisch Amelia J, Edwin Francis, Heckers Stephan, Cohen Bruce M, Patel Tarun B, Carlezon William A
Department of Psychiatry, Harvard Medical School and McLean Hospital, Belmont, Massachusetts 02478, USA.
Biol Psychiatry. 2007 Sep 1;62(5):505-12. doi: 10.1016/j.biopsych.2006.11.014. Epub 2007 Mar 6.
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.
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.
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.
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.
在重度抑郁症和双相情感障碍患者的内侧前额叶皮质(PFC)中发现细胞数量减少,而电休克治疗(ECT)是治疗这些疾病的一种高效方法。我们研究了大鼠接受电惊厥发作(ECS)治疗后即刻及四周后,是否会刺激前额叶皮质中的细胞增殖。同时,我们还检测了ECS是否会改变细胞增殖抑制剂Sprouty2(SPRY2)的表达。
将Sprague-Dawley大鼠进行为期10天的ECS治疗并注射溴脱氧尿苷(BrdU)。在四周的存活期后,我们评估了内侧(边缘下)前额叶皮质(ILPFC)中BrdU、增殖细胞核抗原(PCNA)和SPRY2免疫反应性细胞的密度和数量。我们还确定了对少突胶质细胞、星形胶质细胞、内皮细胞和神经元特异性标志物呈免疫反应的BrdU标记细胞的百分比。
ECS显著增强了边缘下前额叶皮质中新细胞的增殖,且这种效应在治疗后四周持续存在。接受ECS治疗后,表达少突胶质细胞前体细胞标志物的新细胞百分比略有增加。相反,ECS显著减少了表达SPRY2的细胞数量。
ECS刺激了ILPFC内胶质细胞增殖的长期增加。ECS还降低了同一区域中SPRY2的表达,这一效应可能有助于胶质细胞增殖增加。