Single‐Nucleus RNA Sequencing Reveals that Decorin Expression in the Amygdala Regulates Perineuronal Nets Expression and Fear Conditioning Response after Traumatic Brain Injury

Abstract

Traumatic brain injury (TBI) is a risk factor for posttraumatic stress disorder (PTSD). Augmented fear is a defining characteristic of PTSD, and the amygdala is considered the main brain region to process fear. The mechanism by which the amygdala is involved in fear conditioning after TBI is still unclear. Using single‐nucleus RNA sequencing (snRNA‐seq), transcriptional changes in cells in the amygdala after TBI are investigated. In total, 72 328 nuclei are obtained from the sham and TBI groups. 7 cell types, and analysis of differentially expressed genes (DEGs) reveals widespread transcriptional changes in each cell type after TBI are identified. In in vivo experiments, it is demonstrated that Decorin (Dcn) expression in the excitatory neurons of the amygdala significantly increased after TBI, and Dcn knockout in the amygdala mitigates TBI‐associated fear conditioning. Of note, this effect is caused by a Dcn‐mediated decrease in the expression of perineuronal nets (PNNs), which affect the glutamate‐γ‐aminobutyric acid balance in the amygdala. Finally, the results suggest that Dcn functions by interacting with collagen VI α3 (Col6a3). Consequently, the findings reveal transcriptional changes in different cell types of the amygdala after TBI and provide direct evidence that Dcn relieves fear conditioning by regulating PNNs.

Impaired cortical neuronal homeostasis and cognition after diffuse traumatic brain injury are dependent on microglia and type I interferon responses

“…Based on our saturation curve, RNA was sequenced at a depth of 44,000 reads per nuclei using a NovaSeq S4 at the Advanced Genomics Core at The University of Michigan. The experiment design with pooling and replicate numbers for snRNAseq is consistent with previous published studies (Lacar et al, 2016, Gaedcke et al, 2022, Shi et al, 2022, Ko, B., & Van Raamsdonk., 2023, Zhang et al, 2023.…”

scQA: A dual-perspective cell type identification model for single cell transcriptome data

“…Supplementary Fig. S8 illustrates the exclusive expression of certain genes in specific cell types, such as Dlx6os1 , Acsbg1 , Myl9 , which serve as markers in [57] , [58] , [59] , while Hpca exhibits diverse expression patterns across multiple cell types. The protein encoded Hpca is a member of neuron-specific calcium-binding proteins family found in the retina and brain, which plays an important role in various neurons and may express in multiple types of neurons.…”

MicroRNA-124/Death-Associated Protein Kinase 1 Signaling Regulates Neuronal Apoptosis in Traumatic Brain Injury via Phosphorylating NR2B

“…Mice were subjected to either controlled cortical impact (CCI) or sham surgery, as previously described ( Shi et al, 2022 ). First, the mice were deeply anesthetized with isoflurane, and their heads were fixed on a stereotactic device (RWD, China).…”