Enhanced sensitivity of the MRL/MpJ mouse to the neuroplastic and behavioral effects of chronic antidepressant treatments.
Enhanced sensitivity of the MRL/MpJ mouse to the neuroplastic and behavioral effects of chronic antidepressant treatments.
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DOI：
10.1038/npp.2008.234
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发表时间：
2009-06
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影响因子：
--
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中科院分区：
文献类型：
--
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长期服用抗抑郁药物会导致啮齿类动物的神经可塑性和行为发生变化，这种影响可能与临床治疗效果的缓慢出现有关。由于长期抗抑郁治疗对小鼠的影响不确定，这些实验比较了两种近交系小鼠MRL/MpJ和C57 BL/6 J之间的神经发生调节、神经营养因子动员和长期抗抑郁治疗产生的行为。MRL/MpJ品系与增强的伤口愈合和组织再生相关，而C57 BL/6 J小鼠通常用于行为研究。使用流式细胞术测量海马祖细胞的增殖和存活，流式细胞术是一种快速定量BrdU掺入的新平台。在长期给予氟西汀（5，10 mg/kg; i.p.b.i.d.）或地昔帕明（5、10 mg/kg; i.p.b.i.d.）在MRL/MpJ小鼠中持续21天，但在C57 BL/6 J小鼠中不持续。在慢性抗抑郁药治疗之前出生的海马祖细胞在两种小鼠品系中都没有受到影响。MRL/MpJ小鼠脑源性神经营养因子（BDNF）蛋白水平在慢性氟西汀治疗后额叶皮质、海马和杏仁核中显著升高，但仅在额叶皮质中慢性地昔帕明升高。相反，慢性氟西汀治疗后，C57 BL/6 J小鼠除杏仁核外所有区域的BDNF水平均降低，慢性地昔帕明治疗后，脑干的BDNF水平也降低。新颖性引起的食欲减退被用来检查慢性抗抑郁药治疗产生的行为效应。长期给予氟西汀或地昔帕明的MRL/MpJ小鼠在暴露于新环境时比未治疗的小鼠具有显著更短的进食时间，而对C57 BL/6 J小鼠的行为没有影响。总之，长期抗抑郁治疗对海马细胞增殖和BDNF水平的强大影响证实了这些药物在MRL/MpJ小鼠中引起NIH行为变化的能力，但在C57 BL/6 J小鼠中没有产生这些影响。MRL/MpJ小鼠更大的反应性对于药物发现、遗传研究和理解慢性抗抑郁治疗的生理和行为效应的神经机制可能很重要。
Chronic administration of antidepressant drugs produce changes in neuroplasticity and behavior in rodents, effects that may be associated with the slow emergence of clinical therapeutic effects. Because of uncertainty over the effects of chronic antidepressant treatments in mice, these experiments compared the regulation of neurogenesis, mobilization of neurotrophins, and behavior produced by chronic antidepressant treatments between two inbred mouse strains, MRL/MpJ and C57BL/6J. The MRL/MpJ strain is associated with enhanced wound healing and tissue regeneration, whereas C57BL/6J mice are commonly used for behavioral studies. Proliferation and survival of hippocampal progenitor cells were measured using flow cytometry, a new platform that rapidly quantifies BrdU incorporation. Hippocampal cell proliferation was significantly increased following chronic administration of fluoxetine (5, 10 mg/kg; i.p. b.i.d.) or desipramine (5, 10 mg/kg; i.p. b.i.d.) for 21 days in MRL/MpJ mice, but not in C57BL/6J mice. Hippocampal progenitor cells born prior to chronic antidepressant treatments were not affected in either mouse strain. Protein levels of brain-derived neurotrophic factor (BDNF) in MRL/MpJ mice were elevated significantly in the frontal cortex, hippocampus, and amygdala following chronic fluoxetine treatment, but increased only in the frontal cortex by chronic desipramine. In contrast, BDNF levels in C57BL/6J mice were decreased in all regions except for the amygdala after chronic fluoxetine, and were decreased in the brain stem after chronic desipramine. Novelty-induced hypophagia was used to examine a behavioral effect produced by chronic antidepressant treatment. MRL/MpJ mice chronically administered fluoxetine or desipramine had significantly shorter latencies to consume food when exposed to a novel environment than untreated mice, whereas there were no effects on the behavior of C57BL/6J mice. In conclusion, robust effects of chronic antidepressant treatments on hippocampal cell proliferation and BDNF levels paralleled the ability of these drugs to produce changes in NIH behavior in MRL/MpJ, but none of these effects were produced in C57BL/6J mice. The greater responsiveness of MRL/MpJ mice may be important for drug discovery, for genetic studies and for understanding the neural mechanisms underlying the physiological and behavioral effects of chronic antidepressant treatments.
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影响因子：
3.4
作者：
Lucki, I;Dalvi, A;Mayorga, AJ
通讯作者：
Mayorga, AJ
影响因子：
4.7
作者：
Coppell, AL;Pei, Q;Zetterström, TSC
通讯作者：
Zetterström, TSC
影响因子：
10.6
作者：
Caldarone, BJ;Harrist, A;Picciotto, MR
通讯作者：
Picciotto, MR
DOI：
10.1073/pnas.0601992103
发表时间：
2006-05-23
影响因子：
11.1
作者：
Encinas, Juan M.;Vaahtokari, Anne;Enikolopov, Grigori
通讯作者：
Enikolopov, Grigori
影响因子：
8.2
作者：
Balu, Darrick T.;Lucki, Irwin
通讯作者：
Lucki, Irwin