|
| Status |
Public on Dec 15, 2016 |
| Title |
Integrative analysis of disease signatures shows inflammation disrupts juvenile experience-dependent cortical plasticity |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
|
| Summary |
Throughout childhood and adolescence, periods of heightened neuroplasticity are critical for the development of healthy brain function and behavior. Given the high prevalence of neurodevelopmental disorders such as autism, identifying disruptors of developmental plasticity represents an essential step for developing strategies for prevention and intervention. Applying a novel computational approach that systematically assessed connections between 436 transcriptional signatures of disease and multiple signatures of neuroplasticity, we identified inflammation as a common pathological process central to a diverse set of diseases predicted to dysregulate plasticity signatures. We tested the hypothesis that inflammation disrupts developmental cortical plasticity in vivo using the mouse ocular dominance model of experience-dependent plasticity in primary visual cortex. We found administration of systemic lipopolysaccharide suppressed plasticity during juvenile critical period with accompanying transcriptional changes in a particular set of molecular regulators within primary visual cortex. These findings suggest inflammation may have unrecognized adverse consequences on the postnatal developmental trajectory and indicates that treating inflammation may reduce the burden of neurodevelopmental disorders.
|
| |
|
| Overall design |
Comparative RNA expression profiles from juvenile wild-type, adult Lynx1-KO, and adult wild-type bilateral primary visual cortex (n=3 biological replicates per group)
|
| |
|
| Contributor(s) |
Smith MR, Burman P, Sadahiro M, Kidd BA, Dudley JT, Morishita H |
| Citation(s) |
28101530 |
| NIH grant(s) |
| Grant ID |
Grant title |
Affiliation |
Name |
| T32 HD075735 |
Interdisciplinary Training in Systems and Developmental Biology and Birth Defects |
MOUNT SINAI SCHOOL OF MEDICINE |
Ethylin Wang Jabs |
| P30 ES023515 |
The Mount Sinai Transdisciplinary Center on Early Environmental Exposures |
MOUNT SINAI SCHOOL OF MEDICINE |
ROBERT O WRIGHT |
| R01 EY024918 |
Regulation of adult visual cortex plasticity by endogenous nicotinic modulators |
MOUNT SINAI SCHOOL OF MEDICINE |
Morishita |
| R01 EY026053 |
Proteolytic Regulation of Inhibitory Circuits to Gate Cortical Plasticity |
MOUNT SINAI SCHOOL OF MEDICINE |
Morishita |
| R21 MH106919 |
Mechanisms regulating developmental critical period for establishing attention |
MOUNT SINAI SCHOOL OF MEDICINE |
Morishita |
| R01 DK098242 |
Methods for Evolutionary Informed Network Analysis to Discover Disease Variation |
MOUNT SINAI SCHOOL OF MEDICINE |
Joel Thomas Dudley |
| U54 CA189201 |
Mount Sinai's Knowledge Management Center for Illuminating the Druggable Genome |
MOUNT SINAI SCHOOL OF MEDICINE |
Joel Thomas Dudley, Ma'ayan |
|
| |
| Submission date |
Nov 10, 2016 |
| Last update date |
Jan 16, 2019 |
| Contact name |
Milo Robert Smith |
| Organization name |
Icahn School of Medicine at Mount Sinai
|
| Department |
Neuroscience
|
| Lab |
Hirofumi Morishita Laboratory
|
| Street address |
1 Gustave L Levy Place
|
| City |
New York |
| State/province |
NY |
| ZIP/Postal code |
10024 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL6887 |
Illumina MouseWG-6 v2.0 expression beadchip |
|
| Samples (9)
|
|
| Relations |
| BioProject |
PRJNA353100 |
Less...
More...