GSE107357
Forniceal deep brain stimulation induces gene expression and splicing changes that promote neurogenesis and synaptic plasticity
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: There are 13 samples used for RNA-Sequencing, and each is a biological replicate. There are 5 sham (control) samples: 2 wild type sham samples and 3 MeCP2-null samples. There are 8 DBS samples: 4 wildtype and 4 MeCP2-null (KO) samples.