Gene expression atlas of the mouse central nervous system: impact and interactions of age, energy intake and gender.
BACKGROUND
The structural and functional complexity of the mammalian central nervous system (CNS) is organized and modified by complicated molecular signaling processes that are poorly understood.


RESULTS
We measured transcripts of 16,896 genes in 5 CNS regions from cohorts of young, middle-aged and old male and female mice that had been maintained on either a control diet or a low energy diet known to retard aging. Each CNS region (cerebral cortex, hippocampus, striatum, cerebellum and spinal cord) possessed its own unique transcriptome fingerprint that was independent of age, gender and energy intake. Less than 10% of genes were significantly affected by age, diet or gender, with most of these changes occurring between middle and old age. The transcriptome of the spinal cord was the most responsive to age, diet and gender, while the striatal transcriptome was the least responsive. Gender and energy restriction had particularly robust influences on the hippocampal transcriptome of middle-aged mice. Prominent functional groups of age- and energy-sensitive genes were those encoding proteins involved in DNA damage responses (Werner and telomere-associated proteins), mitochondrial and proteasome functions, cell fate determination (Wnt and Notch signaling) and synaptic vesicle trafficking.


CONCLUSIONS
Mouse CNS transcriptomes responded to age, energy intake and gender in a regionally distinctive manner. The systematic transcriptome dataset also provides a window into mechanisms of age-, diet- and sex-related CNS plasticity and vulnerability.
Xu
Xiangru
X
Laboratory of Neurosciences, National Institute on Aging Intramural Research Program, 5600 Nathan Shock Drive, Baltimore, MD 21224, USA. xuxi@grc.nia.nih.gov
Zhan
Ming
M
Duan
Wenzhen
W
Prabhu
Vinayakumar
V
Brenneman
Randall
R
Wood
William
W
Firman
Jeff
J
Li
Huai
H
Zhang
Peisu
P
Ibe
Carol
C
Zonderman
Alan B
AB
Longo
Dan L
DL
Poosala
Suresh
S
Becker
Kevin G
KG
Mattson
Mark P
MP
D000367:Age Factors; D000818:Animals; D002490:Central Nervous System / Q000378:metabolism*; D002149:Energy Intake; D005260:Female; D020869:Gene Expression Profiling; D008297:Male; D051379:Mice; D009473:Neuronal Plasticity; D012333:RNA, Messenger / Q000235:genetics; D012737:Sex Factors
D012333:RNA, Messenger