Early-life iron deficiency anemia alters the development and long-term expression of parvalbumin and perineuronal nets in the rat hippocampus.

Early-life iron deficiency anemia alters the development and long-term expression of parvalbumin and perineuronal nets in the rat hippocampus.
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DOI:
10.1159/000354178
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发表时间:
2013
影响因子:
2.9
通讯作者:
Georgieff MK
Georgieff MK
中科院分区:
医学3区
文献类型:
--
作者:
Callahan LS;Thibert KA;Wobken JD;Georgieff MK

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生命早期缺铁性贫血(IDA)会改变与海马神经元树突结构可塑性相关的关键基因的表达,从而导致大鼠电生理学以及学习和记忆行为的延迟成熟。多个皮质区域的结构成熟的特征是小清蛋白阳性 (PV+) GABA 能中间神经元和神经周围网 (PNN) 的出现。 PV+ 中间神经元和 PNN 的出现可以分别作为关键发育期开始和结束的细胞标记。在此期间,系统从不成熟但高度可塑的状态发展到更成熟和高效的状态,但灵活性较差,并且可能表现出较差的从损伤中恢复的潜力。为了测试胎儿-新生儿 IDA 是否会改变雄性大鼠海马中小清蛋白 (PV) mRNA 表达、蛋白质水平以及 PV+ 中间神经元和 PNN 的数量,从妊娠第 2 天 (G) 到出生后第 (P) 7 天,怀孕母鼠接受缺铁 (ID) 饮食 (3 mg 铁/kg 食物),然后在实验的剩余时间中给予铁充足 (IS) 饮食 (198 mg/kg)。在此方案中,以前的 ID (FID) 动物通过 P56 变得完全铁充足。在 IS 和 ID P7 大鼠中发现了最低水平的 PV(mRNA 和蛋白质)、PV+ 中间神经元和 PNN。到 P15,并持续​​到 P30 和 P65,与 IS 对照相比,ID 大鼠的 PV mRNA 表达和蛋白质水平降低。虽然 P30 或 P65 时 PV+ 神经元的数量没有差异,但与 IS 对照组相比,ID 大鼠中被 PNN 包围的 PV+ 细胞的百分比稍高。 ID组中这些公认的关键期生物标志物的水平较低,这与研究表明急性ID海马成熟较晚以及成年前ID海马可塑性较低的研究一致。这些发现为先前描述的早期 IDA 期间和之后发现的电生理和行为异常提供了额外的潜在细胞基础。
Early-life iron deficiency anemia (IDA) alters the expression of critical genes involved in neuronal dendritic structural plasticity of the hippocampus, thus contributing to delayed maturation of electrophysiology, and learning and memory behavior in rats. Structural maturity in multiple cortical regions is characterized by the appearance of parvalbumin-positive (PV+) GABAergic interneurons and perineuronal nets (PNNs). Appearance of PV+ interneurons and PNNs can serve as cellular markers for the beginning and end of a critical developmental period, respectively. During this period, the system progresses from an immature yet highly plastic condition, to a more mature and efficient state that is however less flexible and may exhibit poorer potential for recovery from injury. To test if fetal-neonatal IDA alters parvalbumin (PV) mRNA expression, protein levels, and the number of PV+ interneurons and PNNs in the male rat hippocampus, pregnant dams were given an iron deficient (ID) diet (3 mg iron/kg chow) from gestational day (G)2 to postnatal day (P)7 and then placed on an iron sufficient (IS) diet (198 mg/kg) for the remainder of the experiment. On this regimen, formerly-ID (FID) animals become fully iron-replete by P56. Minimal levels of PV (mRNA and protein), PV+ interneurons, and PNNs were found in IS and ID P7 rats. By P15, and continuing through P30 and P65, ID rats had reduced PV mRNA expression and protein levels compared to IS controls. While there were no differences in the number of PV+ neurons at either P30 or P65, the percentage of PV+ cells surrounded by PNNs was slightly greater in ID rats as compared to IS controls. The lower levels of these acknowledged critical period biomarkers in the ID group are consistent with studies that demonstrate later maturation of the acutely ID hippocampus and lower plasticity in the adult formerly ID hippocampus. The findings provide additional potential cellular bases for previously described electrophysiologic and behavioral abnormalities found during and following early life IDA.
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