Nicotinamide protects against ethanol-induced apoptotic neurodegeneration in the developing mouse brain.
Nicotinamide protects against ethanol-induced apoptotic neurodegeneration in the developing mouse brain.
复制标题
烟酰胺可预防发育中的小鼠大脑中乙醇诱导的凋亡神经变性。
DOI：
10.1371/journal.pmed.0030101
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发表时间：
2006-04
期刊：
影响因子：
15.8
通讯作者：
Herrera, Daniel G.
中科院分区：
文献类型：
--
作者：
Ieraci, Alessandro;Herrera, Daniel G.
在大脑发育过程中接触酒精可能会导致一种称为胎儿酒精综合征（FAS）的神经系统综合征。乙醇在特定的发育阶段诱导神经元凋亡，特别是在脑生长突增期，这发生在妊娠晚期开始，并在人类出生后持续数年，而在小鼠出生后的前两周发生。在出生后7天（P7）小鼠中给予单剂量乙醇可激活半胱天冬酶-3和前脑中广泛的凋亡性神经元死亡，为在人类FAS中观察到的微脑畸形提供了可能的解释。本研究旨在确定烟酰胺是否可以预防乙醇诱导的神经变性。用单剂量乙醇（5g/kg）处理P7小鼠，并在乙醇暴露后0 h至8 h给予烟酰胺。通过Western印迹分析烟酰胺对乙醇诱导的caspase-3活化和细胞色素-c从线粒体释放的影响（n = 4-7/组）。在扣带皮质、海马CA 1区和丘脑外侧背核中测定Fluoro-Jade B阳性细胞和NeuN阳性细胞的密度（n = 5-6/组）。使用旷场、十字迷宫和恐惧条件反射测试来研究成年小鼠（n = 31-34/组）的行为。烟酰胺还能降低生后小鼠前脑caspase-3的活化（85.14 ± 4.1%）和细胞色素C的释放（80.78 ± 4.39%）。烟酰胺也防止乙醇诱导的细胞凋亡增加。我们证明，乙醇暴露的小鼠表现出受损的性能在恐惧条件反射测试和增加的活动，在开放领域和十字迷宫。给予烟酰胺可预防乙醇暴露小鼠的所有这些行为异常。 我们的研究结果表明，烟酰胺可以防止乙醇对发育中的小鼠大脑的一些有害影响时，给予乙醇暴露后不久。这些结果表明，烟酰胺，已用于治疗糖尿病和大疱性类天疱疮，可能有希望作为FAS的预防性治疗。烟酰胺是一种由患有各种疾病的人类患者常规使用的药物，能够预防胎儿酒精综合征小鼠模型中乙醇暴露的一些神经毒性和行为影响。
Exposure to alcohol during brain development may cause a neurological syndrome called fetal alcohol syndrome (FAS). Ethanol induces apoptotic neuronal death at specific developmental stages, particularly during the brain-growth spurt, which occurs from the beginning of third trimester of gestation and continues for several years after birth in humans, whilst occuring in the first two postnatal weeks in mice. Administration of a single dose of ethanol in 7-d postnatal (P7) mice triggers activation of caspase-3 and widespread apoptotic neuronal death in the forebrain, providing a possible explanation for the microencephaly observed in human FAS. The present study was aimed at determining whether nicotinamide may prevent ethanol-induced neurodegeneration. P7 mice were treated with a single dose of ethanol (5g/kg), and nicotinamide was administered from 0 h to 8 h after ethanol exposure. The effects of nicotinamide on ethanol-induced activation of caspase-3 and release of cytochrome-c from the mitochondria were analyzed by Western blot ( n = 4–7/group). Density of Fluoro-Jade B–positive cells and NeuN-positive cells was determined in the cingulated cortex, CA1 region of the hippocampus, and lateral dorsal nucleus of the thalamus ( n = 5–6/group). Open field, plus maze, and fear conditioning tests were used to study the behavior in adult mice ( n = 31–34/group). Nicotinamide reduced the activation of caspase-3 (85.14 ± 4.1%) and the release of cytochrome-c (80.78 ± 4.39%) in postnatal mouse forebrain, too. Nicotinamide prevented also the ethanol-induced increase of apoptosis. We demonstrated that ethanol-exposed mice showed impaired performance in the fear conditioning test and increased activity in the open field and in the plus maze. Administration of nicotinamide prevented all these behavioral abnormalities in ethanol-exposed mice. Our findings indicate that nicotinamide can prevent some of the deleterious effects of ethanol on the developing mouse brain when given shortly after ethanol exposure. These results suggest that nicotinamide, which has been used in humans for the treatment of diabetes and bullous pemphigoid, may hold promise as a preventive therapy of FAS. Nicotinamide, a drug used routinely by human patients with a variety of conditions, is able to prevent some of the neurotoxic and behavioral effects of ethanol exposure in a mouse model of fetal alcohol syndrome.
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影响因子：
3.8
作者：
Gittins, R;Harrison, PJ
通讯作者：
Harrison, PJ
影响因子：
2.9
作者：
Burd, L;Klug, MG;Kerbeshian, J
通讯作者：
Kerbeshian, J
DOI：
10.1111/j.1530-0277.2000.tb02019.x
发表时间：
2000-04-01
影响因子：
3.2
作者：
Heaton, MB;Mitchell, JJ;Paiva, M
通讯作者：
Paiva, M
DOI：
10.1016/s0304-4165(00)00181-1
发表时间：
2001-02-16
影响因子：
3
作者：
Klaidman, LK;Mukherjee, SK;Adams, JD
通讯作者：
Adams, JD
影响因子：
2.4
作者：
Lin, Shi-Hua;Chong, Zhao Zhong;Maiese, Kenneth
通讯作者：
Maiese, Kenneth