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| Status |
Public on Aug 30, 2018 |
| Title |
The relative contributions of cell-dependent cortical microcircuit aging to cognition and anxiety |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Background: Aging is accompanied by altered thinking (cognition) and feeling (mood) functions that depend to some extent on information processing by brain cortical cell microcircuits. We hypothesized that age-associated long-term functional and biological changes are mediated by gene transcriptomic changes within neuronal cell-types forming cortical microcircuits, namely excitatory pyramidal cells (PYC) and inhibitory GABAergic neurons expressing vasoactive intestinal peptide (Vip), somatostatin (Sst) and parvalbumin (Pvalb).
Methods: To test this hypothesis, we assessed locomotor, anxiety-like and cognitive behavioral changes between young (2 months, n=9) and old (22 months, n=12) male C57BL/6 mice, and performed frontal cortex cell-type specific molecular profiling, using laser-capture microscopy and RNA sequencing.
Results: Old-mice displayed increased anxiety and reduced working memory. The four cell-types displayed distinct age-related transcriptomes and biological pathway profiles, affecting metabolic and cell signaling pathways, and selective markers of neuronal vulnerability (Ryr3), resilience (Oxr1), and mitochondrial dynamics (Opa1), suggesting high age-related vulnerability of PYCs, and variable degree of adaptation in GABAergic neurons. Correlations between gene expression and behaviors suggest that changes in cognition and anxiety associated with age are partly mediated by normal age-related cell changes, and that additional age-independent decreases in synaptic and signaling pathways, notably in PYC and SST-neurons further contribute to behavioral changes.
Conclusions: Our study demonstrates cell-dependent differential vulnerability and coordinated cell-specific cortical microcircuit molecular changes with age. Collectively, the results suggest intrinsic molecular links between aging, cognition and mood-related behaviors with SST-neurons contributing evenly to both behavioral conditions.
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| Overall design |
Male C57BL/6 mice, Young (2 months, n=9) and old (22 months, n=12), performed frontal cortex cell-type specific molecular profiling, using laser-capture microscopy and RNA sequencing using illumina HiSeq
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| Contributor(s) |
Shukla R, Prevot TD, French L, Isserlin R, Rocco BR, Banasr M, Bader GD, Sibille E |
| Citation(s) |
30446205 |
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| Submission date |
Aug 29, 2018 |
| Last update date |
Mar 21, 2019 |
| Contact name |
Etienne Sibille |
| E-mail(s) |
Etienne.Sibille@camh.ca
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| Phone |
416-535-8501
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| Organization name |
Center for Addiction and Mental Health
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| Department |
Neuroscience of Aging and Depression
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| Lab |
Sibille Lab
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| Street address |
RM,133, 250 college street
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| City |
Toronto |
| State/province |
Ontario |
| ZIP/Postal code |
M5T1R8 |
| Country |
Canada |
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| Platforms (1) |
| GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
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| Samples (83)
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| Relations |
| BioProject |
PRJNA488384 |
| SRA |
SRP159067 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE119183_RawCounts.txt.gz |
2.3 Mb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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