Morphine-enhanced apoptosis in selective brain regions of neonatal rats.
Morphine-enhanced apoptosis in selective brain regions of neonatal rats.
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DOI：
10.1016/j.ijdevneu.2013.02.009
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发表时间：
2013-06
期刊：
影响因子：
--
通讯作者：
Soriano SG
中科院分区：
文献类型：
--
作者：
Bajic D;Commons KG;Soriano SG
新生儿长期接触阿片类药物与以下方面有关：抗伤害耐受性、长期神经发育延迟、认知和运动障碍。在体外研究中，吗啡也被证明可以诱导细胞凋亡，但它在发育中的大鼠大脑中的体内作用尚不清楚。因此，我们假设，在抗伤害性耐受和依赖的新生大鼠模型中，延长吗啡给药时间与增加神经细胞凋亡有关。我们分析了以下几组新生大鼠：(1)单纯组(n=6)；(2)对照组(生理盐水，n=5)；(3)吗啡组(n=8)。从出生后第1天开始，皮下注射硫酸吗啡或等量生理盐水，每日2次，连续6.5天。第7天用热板法测定大鼠的抗伤害耐受性。Caspase-3裂解免疫荧光结合特异性标记物确定神经元和神经胶质细胞凋亡的证据。在PD7，给予吗啡6天半后，皮质和杏仁核的凋亡细胞密度显著增加，但在海马区、下丘脑和中脑导水管周围灰质没有明显变化。凋亡细胞表现出与神经元相似的形态。无论治疗方法如何，只有极少数单个小胶质细胞呈caspase-3阳性，而星形胶质细胞则不呈阳性。综上所述，新生大鼠(PD1-7)反复注射吗啡与不同解剖区域脊髓上细胞凋亡的增加有关，这些区域对感觉(皮质)和情绪记忆处理(杏仁核)具有重要作用。对学习很重要的大脑区域(海马体)以及自主神经和伤害性信息处理(下丘脑和中脑导水管周围灰质)没有受到影响。反复注射吗啡后，缺乏广泛的胶质细胞凋亡或强大的胶质细胞激活，这表明胶质细胞在这个早期可能不会受到慢性吗啡的影响。未来的研究应该调查长期给予吗啡的新生大鼠模型中表现出的与细胞凋亡增强相关的长期行为后遗症。
Prolonged neonatal opioid exposure has been associated with: antinociceptive tolerance, long-term neurodevelopmental delay, cognitive, and motor impairment. Morphine has also been shown to induce apoptotic cell death in vitro studies, but its in-vivo effect in developing rat brain is unknown. Thus, we hypothesized that prolongued morphine administration in neonatal rats in a model of antinociceptive tolerance and dependence is associated with increased neuroapoptosis. We analyzed neonatal rats from the following groups (1) naïve group (n=6); (2) control group (normal saline (NS), n=5), and (3) morphine group (n=8). Morphine sulfate or equal volume of NS was injected subcutaneously twice daily for 6.5 days starting on postnatal day (PD) 1. Development of antinociceptive tolerance was confirmed by Hot Plate test on the 7th day. Evidence of neuronal and glial apoptosis was determined by cleaved caspase-3immunofluorescence combined with specific markers. At PD7, morphine administration after 6 ½ days significantly increased the density of apoptotic cells in the cortex and amygdala, but not in the hippocampus, hypothalamus, or periaqueductal gray. Apoptotic cells exhibited morphology analogous to neurons. Irrespective of the treatment, only a very few individual microglia but not astrocytes were caspase-3 positive. In summary, repeated morphine administration in neonatal rats (PD1-7) is associated with increased supraspinal apoptosis in distinct anatomical regions known to be important for sensory (cortex) and emotional memory processing (amygdala). Brain regions important for learning (hippocampus), and autonomic and nociceptive processing (hypothalamus and periaqueductal gray) were not affected. Lack of widespread glial apoptosis or robust glial activation following repeated morphine administration suggests that glia might not be affected by chronic morphine at this early age. Future studies should investigate long-term behavioral sequelae of demonstrated enhanced apoptosis associated with prolonged morphine administration in a neonatal rat model.
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影响因子：
168.9
作者：
Anand, KJS;Hall, RW;Barton, BA
通讯作者：
Barton, BA
DOI：
10.1002/tera.1420310203
发表时间：
1985-01-01
期刊：
TERATOLOGY
影响因子：
--
作者：
BOOZE, RM;MACTUTUS, CF
通讯作者：
MACTUTUS, CF
影响因子：
2.5
作者：
Che, Y;Sun, HY;Ma, YY
通讯作者：
Ma, YY
影响因子：
10.6
作者：
Davidson, RJ
通讯作者：
Davidson, RJ
影响因子：
8.2
作者：
Andersen, SL
通讯作者：
Andersen, SL