Czéh Boldizsár, Welt Tobias, Fischer Anja K, Erhardt Angelika, Schmitt Wolfram, Müller Marianne B, Toschi Nicola, Fuchs Eberhard, Keck Martin E
The German Primate Center, Division of Neurobiology, Göttingen, Germany.
Biol Psychiatry. 2002 Dec 1;52(11):1057-65. doi: 10.1016/s0006-3223(02)01457-9.
Repetitive transcranial magnetic stimulation is increasingly used as a therapeutic tool in psychiatry and has been demonstrated to attenuate the activity of the stress hormone system. Stress-induced structural remodeling in the adult hippocampus may provide a cellular basis for understanding the impairment of neural plasticity in depressive illness. Accordingly, reversal of structural remodeling might be a desirable goal for antidepressant therapy. The present study investigated the effect of chronic psychosocial stress and concomitant repetitive transcranial magnetic stimulation treatment on stress hormone regulation and hippocampal neurogenesis.
Adult male rats were submitted to daily psychosocial stress and repetitive transcranial magnetic stimulation (20 Hz) for 18 days. Cell proliferation in the dentate gyrus was quantified by using BrdU immunohistochemistry, and both the proliferation rate of progenitors and the survival rate of BrdU-labeled cells were evaluated. To characterize the activity of the hypothalamic-pituitary-adrenocortical system, plasma corticotropin and corticosterone concentrations were measured.
Chronic psychosocial stress resulted in a significant increase of stress hormone levels and potently suppressed the proliferation rate and survival of the newly generated hippocampal granule cells. Concomitant repetitive transcranial magnetic stimulation treatment normalized the stress-induced elevation of stress hormones; however, despite the normalized activity of the hypothalamic-pituitary-adrenocortical system, the decrement of hippocampal cell proliferation was only mildly attenuated by repetitive transcranial magnetic stimulation, while the survival rate of BrdU-labeled cells was further suppressed by the treatment.
These results support the notion that attenuation of the hypothalamic-pituitary-adrenocortical system is an important mechanism underlying the clinically observed antidepressant effect of repetitive transcranial magnetic stimulation, whereas this experimental design did not reveal beneficial effects of repetitive transcranial magnetic stimulation on adult hippocampal neurogenesis.
重复经颅磁刺激越来越多地被用作精神病学中的一种治疗工具，并且已被证明可减弱应激激素系统的活性。应激诱导的成年海马体结构重塑可能为理解抑郁症中神经可塑性受损提供细胞基础。因此，逆转结构重塑可能是抗抑郁治疗的一个理想目标。本研究调查了慢性心理社会应激以及同时进行的重复经颅磁刺激治疗对应激激素调节和海马神经发生的影响。
成年雄性大鼠每天接受心理社会应激和重复经颅磁刺激（20赫兹），持续18天。通过使用BrdU免疫组织化学对齿状回中的细胞增殖进行定量，并评估祖细胞的增殖率和BrdU标记细胞的存活率。为了表征下丘脑 - 垂体 - 肾上腺皮质系统的活性，测量血浆促肾上腺皮质激素和皮质酮浓度。
慢性心理社会应激导致应激激素水平显著升高，并有力地抑制了新生成的海马颗粒细胞的增殖率和存活率。同时进行的重复经颅磁刺激治疗使应激诱导的应激激素升高恢复正常；然而，尽管下丘脑 - 垂体 - 肾上腺皮质系统的活性恢复正常，但重复经颅磁刺激仅轻微减轻了海马细胞增殖的减少，而该治疗进一步抑制了BrdU标记细胞的存活率。
这些结果支持以下观点，即下丘脑 - 垂体 - 肾上腺皮质系统的减弱是重复经颅磁刺激临床观察到的抗抑郁作用的重要机制，而这种实验设计未揭示重复经颅磁刺激对成年海马神经发生的有益作用。
