Impacts of forebrain neuronal glycine transporter 1 disruption in the senescent brain: evidence for age-dependent phenotypes in Pavlovian learning.
Impacts of forebrain neuronal glycine transporter 1 disruption in the senescent brain: evidence for age-dependent phenotypes in Pavlovian learning.
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DOI：
10.1037/a0021556
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发表时间：
2010-12
影响因子：
1.9
通讯作者：
Yee, Benjamin K.
中科院分区：
文献类型：
--
作者：
Dubroqua, Sylvain;Singer, Philipp;Boison, Detlev;Feldon, Joram;Moehler, Hanns;Yee, Benjamin K.
前脑神经元中甘氨酸转运蛋白1 （GlyT1）的遗传缺失导致多种前认知表型，可能是由于n -甲基-d-天冬氨酸受体（NMDAR）功能增强所致。然而，对突触甘氨酸终生升高可能产生的有害兴奋毒性作用的担忧已经提出。这些影响可能会加速衰老过程，削弱甚至逆转成年期的前认知表型。在这里，我们研究了突变小鼠系（CamKIIαCre;GlyT1tm1.2fl/fI）中最强大的表型之一，即增强的厌恶巴甫洛夫条件反射，是否会随着年龄的增长而改变。3个月大（成人）和22个月大（老年）突变体之间的比较证实了这两个年龄段都存在这种表型。然而，巴甫洛夫表型的时间表达在衰老时发生了改变；成年突变体表现出明显的会话内灭绝，而老年突变体则没有。免疫组化检测同一动物NMDAR NR2B亚基的表达及神经细胞增殖。正如预期的那样，这些在老年小鼠中减少了，但没有因突变而加剧。因此，我们的研究结果并没有证实对前脑神经元终身GlyT1破坏的神经毒性作用的担忧，但为表型表达的改变作为年龄的函数提供了证据。后一点提出了进一步研究该突变系在成年期发现的其他促认知表型的必要性。此外，我们在这里首次揭示了突变体海马中未成熟神经元数量的明显增加，尽管这种表型的行为意义仍有待确定。
Genetic deletion of glycine transporter 1 (GlyT1) in forebrain neurons gives rise to multiple pro-cognitive phenotypes, presumably due to enhanced N-methyl-d-aspartate receptor (NMDAR) functions. However, concerns over possible harmful excitotoxic effects under life-long elevation of synaptic glycine have been raised. Such effects might accelerate the aging process, weakening or even reversing the pro-cognitive phenotypes identified in adulthood. Here, we examined if one of the most robust phenotypes in the mutant mouse line (CamKIIαCre;GlyT1tm1.2fl/fI), namely, enhanced aversive Pavlovian conditioning, might be modified by age. Comparison between 3-month-old (adult) and 22-month-old (aged) mutants confirmed the presence of this phenotype at both ages. However, the temporal expression of the Pavlovian phenotype was modified in senescence; while adult mutants showed a pronounced within-session extinction, aged mutants did not. Expression of NR2B subunits of NMDAR and neural proliferation were examined in the same animals by immunohistochemistry. These were reduced in the aged mice as expected, but not exacerbated by the mutation. Thus, our results do not substantiate the concerns of neurotoxic effects through life-long GlyT1 disruption in forebrain neurons, but provide evidence for a modification of phenotypic expression as a function of age. The latter points raise the need to further investigate other pro-cognitive phenotypes identified at adulthood in this mutant line. In addition, we revealed here for the first time a clear increase in the number of immature neurons in the hippocampus of the mutants, although the behavioral significance of this phenotype remains to be determined.
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影响因子：
7.6
作者：
Depoortère, R;Dargazanli, G;Scatton, B
通讯作者：
Scatton, B
影响因子：
3
作者：
Richmond, MA;Murphy, CA;Feldon, J
通讯作者：
Feldon, J
影响因子：
4.2
作者：
Rami, A;Jansen, S;Winckler, J
通讯作者：
Winckler, J
成人的海马牙齿颗粒细胞正在进行成熟，调节大脑中的学习和记忆。
DOI：
10.1523/jneurosci.3362-09.2009
发表时间：
2009-10-28
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Deng W;Saxe MD;Gallina IS;Gage FH
通讯作者：
Gage FH
影响因子：
1.8
作者：
CONOVER, WJ;IMAN, RL
通讯作者：
IMAN, RL