Genetically determined measures of striatal D2 signaling predict prefrontal activity during working memory performance.
Genetically determined measures of striatal D2 signaling predict prefrontal activity during working memory performance.
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DOI：
10.1371/journal.pone.0009348
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发表时间：
2010-02-22
期刊：
影响因子：
3.7
通讯作者：
Rubini G
中科院分区：
文献类型：
--
作者：
Bertolino A;Taurisano P;Pisciotta NM;Blasi G;Fazio L;Romano R;Gelao B;Lo Bianco L;Lozupone M;Di Giorgio A;Caforio G;Sambataro F;Niccoli-Asabella A;Papp A;Ursini G;Sinibaldi L;Popolizio T;Sadee W;Rubini G
编码D2受体（DRD 2）的基因变异与精神分裂症和工作记忆缺陷的风险有关。功能性内含子SNP（rs 1076560）预测两种D2受体亚型D2 S（主要是突触前）和D2 L（主要是突触后）的相对表达。然而，DRD 2的功能性遗传变异对纹状体多巴胺D2信号传导的影响及其与人类工作记忆过程中前额叶活动的相关性尚不清楚。对37名健康受试者进行rs 1076560（G>T）基因分型，并使用[123 I]IBZM（主要与突触后D2受体结合）和[123 I]FP-CIT（与突触前多巴胺转运蛋白结合，其活性和密度也受突触前D2受体调节）进行SPECT，以及在N-Back工作记忆期间进行BOLD fMRI。携带T等位基因（先前与D2 S表达降低相关）的受试者纹状体[123 I]IBZM和[123 I]FP-CIT结合降低。DRD 2基因型也不同程度地预测了纹状体多巴胺D2信号传导与多巴胺受体之间的相关性。（如通过两种放射性示踪剂的因子分析所确定的）和前额叶皮层在工作记忆期间的活动，如通过BOLD fMRI所测量的，我们的研究结果表明，DRD 2中的这一功能性SNP预测了两种放射性示踪剂与多巴胺转运蛋白和D2受体的纹状体结合以及纹状体D2信号与工作记忆任务执行期间前额叶皮层活动之间的相关性。这些数据是一致的可能性，纹状体神经元的兴奋性/抑制性调制的平衡也可能影响纹状体输出与前额叶活动的皮质-纹状体-丘脑-皮质通路内的工作记忆性能。
Variation of the gene coding for D2 receptors (DRD2) has been associated with risk for schizophrenia and with working memory deficits. A functional intronic SNP (rs1076560) predicts relative expression of the two D2 receptors isoforms, D2S (mainly pre-synaptic) and D2L (mainly post-synaptic). However, the effect of functional genetic variation of DRD2 on striatal dopamine D2 signaling and on its correlation with prefrontal activity during working memory in humans is not known. Thirty-seven healthy subjects were genotyped for rs1076560 (G>T) and underwent SPECT with [123I]IBZM (which binds primarily to post-synaptic D2 receptors) and with [123I]FP-CIT (which binds to pre-synaptic dopamine transporters, whose activity and density is also regulated by pre-synaptic D2 receptors), as well as BOLD fMRI during N-Back working memory. Subjects carrying the T allele (previously associated with reduced D2S expression) had striatal reductions of [123I]IBZM and of [123I]FP-CIT binding. DRD2 genotype also differentially predicted the correlation between striatal dopamine D2 signaling (as identified with factor analysis of the two radiotracers) and activity of the prefrontal cortex during working memory as measured with BOLD fMRI, which was positive in GG subjects and negative in GT. Our results demonstrate that this functional SNP within DRD2 predicts striatal binding of the two radiotracers to dopamine transporters and D2 receptors as well as the correlation between striatal D2 signaling with prefrontal cortex activity during performance of a working memory task. These data are consistent with the possibility that the balance of excitatory/inhibitory modulation of striatal neurons may also affect striatal outputs in relationship with prefrontal activity during working memory performance within the cortico-striatal-thalamic-cortical pathway.
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DOI：
10.1523/jneurosci.4858-08.2009
发表时间：
2009-01-28
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Bertolino A;Fazio L;Di Giorgio A;Blasi G;Romano R;Taurisano P;Caforio G;Sinibaldi L;Ursini G;Popolizio T;Tirotta E;Papp A;Dallapiccola B;Borrelli E;Sadee W
通讯作者：
Sadee W
影响因子：
17.7
作者：
Callicott, JH;Egan, MF;Weinberger, DR
通讯作者：
Weinberger, DR
影响因子：
17.7
作者：
Callicott, JH;Mattay, VS;Weinberger, DR
通讯作者：
Weinberger, DR
影响因子：
10.6
作者：
Bertolino, A;Blasi, G;Nardini, M
通讯作者：
Nardini, M
影响因子：
30.8
作者：
Allen, Nicole C.;Bagade, Sachin;Bertram, Lars
通讯作者：
Bertram, Lars