Sex-related long-term behavioral and hippocampal cellular alterations after nociceptive stimulation throughout postnatal development in rats
Sex-related long-term behavioral and hippocampal cellular alterations after nociceptive stimulation throughout postnatal development in rats
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DOI：
10.1016/j.neuropharm.2013.10.007
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发表时间：
2014-02-01
影响因子：
4.7
通讯作者：
Covolan, Luciene
中科院分区：
文献类型：
--
作者：
Lima, Marcia;Malheiros, Jackeline;Covolan, Luciene
早期伤害性刺激可改变成年大鼠齿状回的神经发生率和行为库。本研究评价了在不同发育阶段施加伤害性刺激对40日龄男女青少年伤害性和焦虑样行为、海马激活、细胞增殖、海马BDNF和血浆皮质酮水平的长期影响。在出生后第1天（P1组）、第8天（P8组）或第21天（P21组）足底注射完全弗氏佐剂（CFA）诱导免疫刺激。对照组动物不受任何刺激。在P21，每组动物的一个子集接受BrdU，并在P40灌注，以鉴定齿状回颗粒细胞层中的增殖细胞。另一组大鼠在P40进行行为测试，一周后进行磁共振成像（MRI）采集。疼痛刺激诱发青少年的痛觉减退，主要是女性（P < 0.02），反映在热板试验中比对照组有更长的缩爪潜伏期和更少的舔爪（P < 0.001）。这也导致更多的时间花在张开的双臂上，例如，焦虑样行为显著低于对照组（P < 0.01），尤其是女性（P < 0.01）。海马齿状回的增殖细胞率在P8时男女均最高（P < 0.001），P1和PS时雄性比雌性增殖更多，与海马BDNF水平呈正相关，与血浆皮质酮呈负相关。锰增强MRI信号也存在性别差异，P1时女性比男性更明显（P < 0.01）。这项研究是在细胞基础上研究新生儿伤害性刺激的性别依赖性长期后果的第一步。(C)2013爱思唯尔有限公司保留所有权利。
Early noxious stimuli may alter the neurogenesis rate in the dentate gyrus and the behavioral repertoire of adult rats. This study evaluated the long-term effects of noxious stimulation, imposed in different phases of development, on nociceptive and anxiety-like behaviors, hippocampal activation, cell proliferation, hippocampal BDNF and plasma corticosterone levels in 40 day-old male and female adolescents. Noxious stimulation was induced by intra-plantar injection of Complete Freund's adjuvant (CFA), on postnatal days (P) 1 (group P1), 8 (P8) or 21 (P21). Control animals were not stimulated in any way. On P21 a subset of animals from each group received BrdU and was perfused on P40 for identification of proliferating cells in the granule cell layer of the dentate gyrus. Another subset of rats was subjected to behavioral testing on P40 and one week later, to magnetic resonance imaging (MRI) acquisition. Noxious stimulation evoked hypoalgesia in adolescents, mainly in females (P < 0.02), reflected by greater latency to withdraw the paw and less paw lickings in the hot plate test than controls (P < 0.001). It also resulted in more time spent in the open arms, e.g., less anxiety-like behavior than controls (P < 0.01), especially in females (P < 0.01, compared with males). Proliferative cell rate in the dentate gyrus was the highest in P8 males and females (P < 0.001), with males exhibiting more proliferation than females on P1 and PS, which was directly related to the hippocampal levels of BDNF and inversely related to plasma corticosterone. Sex differences were also detected in manganese-enhanced MRI signal, which was more prominent in P1 females than males (P < 0.01). This study represents the first step of investigation on the cellular basis of the sex-dependent long-term consequences of nociceptive stimuli in newborns. (C) 2013 Elsevier Ltd. All rights reserved.