Zhang Liqun, Blomgren Klas, Kuhn H Georg, Cooper-Kuhn Christi M
Center for Brain Repair and Rehabilitation, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Sweden.
Neurobiol Dis. 2009 May;34(2):366-74. doi: 10.1016/j.nbd.2009.02.006. Epub 2009 Feb 20.
This study addressed the influence of propylthiouracil (PTU)-induced hypothyroidism on postnatal and adult neurogenesis. PTU was administered from birth to postnatal day 10 (P10) or P21, leading to decreased neural stem cell/progenitor proliferation in the dentate gyrus, as well as significantly fewer granule cells and reduced hippocampal volume. Upon P22 PTU withdrawal, plasma thyroid hormone levels were normal by P90, there was no difference in the number of dentate gyrus or subventricular proliferating cells, but brain weight was smaller. In addition, dentate gyrus density of surviving BrdU-labeled cells increased, with no changes to the olfactory bulb. Quantitative PCR revealed decreased FGF-2, NGF, Wnt3a, and VEGF-A hippocampal expression during PTU treatment, with recovery in adulthood. Pro-apoptotic Bax was up-regulated, and anti-apoptotic Bcl-2 was down-regulated, during PTU treatment, both of which were normalized in the adult brain. In contrast, apoptosis-inducing factor (AIF) was down-regulated in the adult. These results suggest that mechanisms in the adult brain attempt to compensate for decreased neurogenesis due to postnatal hypothyroidism.
本研究探讨了丙硫氧嘧啶（PTU）诱导的甲状腺功能减退对出生后及成年期神经发生的影响。从出生至出生后第10天（P10）或第21天给予PTU，导致齿状回神经干细胞/祖细胞增殖减少，颗粒细胞数量显著减少，海马体积减小。在P22停用PTU后，到P90时血浆甲状腺激素水平恢复正常，齿状回或脑室下增殖细胞数量无差异，但脑重量较小。此外，存活的BrdU标记细胞的齿状回密度增加，嗅球无变化。定量PCR显示，PTU治疗期间海马中FGF-2、NGF、Wnt3a和VEGF-A的表达降低，成年期恢复。PTU治疗期间促凋亡蛋白Bax上调，抗凋亡蛋白Bcl-2下调，两者在成年大脑中均恢复正常。相反，凋亡诱导因子（AIF）在成年期下调。这些结果表明，成年大脑中的机制试图补偿由于出生后甲状腺功能减退导致的神经发生减少。
