Diurnal rhythms across the human dorsal and ventral striatum

被引:30
作者
Ketchesin, Kyle D. [1 ]
Zong, Wei [2 ]
Hildebrand, Mariah A. [1 ]
Seney, Marianne L. [1 ]
Cahill, Kelly M. [2 ]
Scott, Madeline R. [1 ]
Shankar, Vaishnavi G. [1 ]
Glausier, Jill R. [1 ]
Lewis, David A. [1 ]
Tseng, George C. [2 ]
McClung, Colleen A. [1 ]
机构
[1] Univ Pittsburgh, Dept Psychiat, Translat Neurosci Program, Sch Med, Pittsburgh, PA 15219 USA
[2] Univ Pittsburgh, Dept Biostat, Pittsburgh, PA 15213 USA
关键词
human postmortem; circadian rhythms; striatum; gene expression; CIRCADIAN PATTERNS; GENE-EXPRESSION; BASAL GANGLIA; RNAS; TASKS;
D O I
10.1073/pnas.2016150118
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
The human striatum can be subdivided into the caudate, putamen, and nucleus accumbens (NAc). Each of these structures have some overlapping and some distinct functions related to motor control, cognitive processing, motivation, and reward. Previously, we used a "time-of-death" approach to identify diurnal rhythms in RNA transcripts in human cortical regions. Here, we identify molecular rhythms across the three striatal subregions collected from post-mortem human brain tissue in subjects without psychiatric or neurological disorders. Core circadian clock genes are rhythmic across all three regions and show strong phase concordance across regions. However, the putamen contains a much larger number of significantly rhythmic transcripts than the other two regions. Moreover, there are many differences in pathways that are rhythmic across regions. Strikingly, the top rhythmic transcripts in NAc (but not the other regions) are predominantly small nucleolar RNAs and long noncoding RNAs, suggesting that a completely different mechanism might be used for the regulation of diurnal rhythms in translation and/or RNA processing in the NAc versus the other regions. Further, although the NAc and putamen are generally in phase with regard to timing of expression rhythms, the NAc and caudate, and caudate and putamen, have several clusters of discordant rhythmic transcripts, suggesting a temporal wave of specific cellular processes across the striatum. Taken together, these studies reveal distinct transcriptome rhythms across the human striatum and are an important step in helping to understand the normal function of diurnal rhythms in these regions and how disruption could lead to pathology.
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页数:11
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