|
| Status |
Public on Apr 17, 2018 |
| Title |
Forniceal deep brain stimulation induces gene expression and splicing changes that promote neurogenesis and plasticity |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Clinical trials are currently underway to assess the efficacy of forniceal deep brain stimulation (DBS) for the improvement of memory in Alzheimer’s patients, and forniceal DBS has been shown to improve learning and memory in a mouse model of Rett syndrome (RTT), an intellectual disability disorder. The mechanism of DBS benefits has been elusive, however, so we assessed gene expression, splice isoform abundance, DNA methylation, and proteomic changes following acute forniceal DBS in wild-type mice and a mouse model lacking Mecp2, the gene whose loss of function causes RTT. We found that DBS upregulates genes involved in synaptic function, cell survival, and neurogenesis, and alters the proportions of different isoforms even for genes whose expression is unchanged. DBS rescued ~25% of the gene expression defects in Mecp2-null mice, particularly those involved in synaptic components, and it induced expression of 17-24% of the genes found to be downregulated in intellectual disability mouse models and in post-mortem human brain tissue from patients with Major Depressive Disorder. DBS could thus benefit individuals with a variety of neuropsychiatric disorders.
|
| |
|
| Overall design |
mRNA-Sequencing was performed on dentate gyrus tissue from wild type (WT) and MeCP2-heterozygous (Het) females. There are two treatment groups: sham treated (unstimulated) and deep brain stimulation (DBS) treated. Each sample is a biological replicate. There are 7 Het samples: 3 sham treated, 4 DBS treated. There are 8 WT samples: 4 sham treated and 4 DBS treated.
|
| |
|
| Contributor(s) |
Pohodich AE, Yalamanchili H, Liu Z, Zoghbi H |
| Citation(s) |
29570050 |
| |
| Submission date |
Mar 12, 2018 |
| Last update date |
Mar 21, 2019 |
| Contact name |
Hari Krishna Yalamanchili |
| E-mail(s) |
hari.yalamanchili@bcm.edu
|
| Organization name |
Baylor College of Medicine
|
| Street address |
1250 Moursund St #1125,
|
| City |
Houston, |
| State/province |
TX |
| ZIP/Postal code |
77030 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
|
| Samples (15)
|
|
| Relations |
| BioProject |
PRJNA437923 |
| SRA |
SRP134938 |
Less...
More...