Physical Exercise and Antidepressants Enhance BDNF Targeting in Hippocampal CA3 Dendrites: Further Evidence of a Spatial Code for BDNF Splice Variants
Physical Exercise and Antidepressants Enhance BDNF Targeting in Hippocampal CA3 Dendrites: Further Evidence of a Spatial Code for BDNF Splice Variants
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DOI：
10.1038/npp.2012.5
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发表时间：
2012-06-01
影响因子：
7.6
通讯作者：
Tongiorgi, Enrico
中科院分区：
文献类型：
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作者：
Baj, Gabriele;D'Alessandro, Valentina;Tongiorgi, Enrico
脑源性神经营养因子（BDNF）由多个BDNF转录本编码，其功能尚不清楚。我们最近的研究表明，BDNF转录本的一个子集可以响应电活动进入远端树突，而其他转录本则被隔离到躯体近端区域。体育锻炼和抗抑郁治疗通过上调BDNF发挥其有益作用，BDNF是支持新生齿状回（DG）神经元存活和分化所必需的。虽然这些DG过程是抗抑郁作用所必需的，但CA1在抗抑郁作用中的作用已被排除，而且对CA3神经元的影响仍不清楚。在这里，我们首次表明体育锻炼和抗抑郁药物可诱导CA3中BDNF的局部增加。连续28天的自愿体育锻炼，或每天10 mg/kg氟西汀或瑞波西汀治疗2周，使整个海马神经元体中BDNF mRNA和蛋白的整体增加，CA3神经元树突中BDNF的特异性增加。这种增加是由BDNF外显子6变异引起的。在培养的海马神经元中，应用5 -羟色胺或去甲肾上腺素（10-50 μ M）可诱导突触传递增加，并在树突中靶向BDNF mRNA。抗抑郁药物或运动后CA3树突中BDNF表达的增加进一步支持了抗抑郁药物作用的神经营养因子假说，并证实了BDNF mRNA剪接变体的差异亚细胞定位为BDNF在特定亚细胞区域的选择性表达提供了空间编码。这种选择性表达可能被用来设计更具体的抗抑郁药。神经精神药理学杂志（2012）37,1600-1611；doi: 10.1038 / npp.2012.5;2012年2月8日在线发布
Brain-derived neurotrophic factor (BDNF) is encoded by multiple BDNF transcripts, whose function is unclear. We recently showed that a subset of BDNF transcripts can traffic into distal dendrites in response to electrical activity, while others are segregated into the somatoproximal domains. Physical exercise and antidepressant treatments exert their beneficial effects through upregulation of BDNF, which is required to support survival and differentiation of newborn dentate gyrus (DG) neurons. While these DG processes are required for the antidepressant effect, a role for CA1 in antidepressant action has been excluded, and the effect on CA3 neurons remains unclear. Here, we show for the first time that physical exercise and antidepressants induce local increase of BDNF in CA3. Voluntary physical exercise for 28 consecutive days, or 2-week treatment with 10 mg/kg per day fluoxetine or reboxetine, produced a global increase of BDNF mRNA and protein in the neuronal somata of the whole hippocampus and a specific increase of BDNF in dendrites of CA3 neurons. This increase was accounted for by BDNF exon 6 variant. In cultured hippocampal neurons, application of serotonin or norepinephrine (10-50 mu M) induced increase in synaptic transmission and targeting of BDNF mRNA in dendrites. The increased expression of BDNF in CA3 dendrites following antidepressants or exercise further supports the neurotrophin hypothesis of antidepressants action and confirms that the differential subcellular localization of BDNF mRNA splice variants provides a spatial code for a selective expression of BDNF in specific subcellular districts. This selective expression may be exploited to design more specific antidepressants. Neuropsychopharmacology (2012) 37, 1600-1611; doi:10.1038/npp.2012.5; published online 8 February 2012