What Causes Memory Deficit in Certain Types of Epilepsy? Bulk and Single Nucleus RNA-Seq Tell Different Stories

In this article:

  • The underlying mechanisms of memory deficits in temporal lobe epilepsy
  • How differences between bulk and single cell RNA sequencing can affect results

What is Temporal Lobe Epilepsy (TLE)?

Epilepsy is one of the most common neurological conditions in the world. An epileptic seizure is caused by an imbalance between the two main types of neuron activity- excitatory and inhibitory. The balance between them can be disrupted by a variety of genetic, immune, metabolic and many other factors. 

Temporal Lobe Epilepsy (TLE) is a distinct subtype of epilepsy. Along with not being allowed to drive, in severe cases, some patients may opt to have the seizure-prone regions of their temporal lobe surgically removed. Some patients report memory deficits among the most debilitating symptoms, while others do not have their memory affected as severely by their TLE, and little is known about the underlying mechanisms behind memory dysfunction in TLE.

Single Cell Analysis Uncovers Disruption to Genes Related to Memory Formation

In a recent paper in npj Genomic Medicine, Busch et al. analysed cortical tissue samples from 6 patients with TLE, comparing those patients with and without memory deficits. Using machine learning to identify enriched signalling pathways, they found that genes associated with synapse growth (synaptogenesis) in both excitatory and inhibitory neurons were over expressed in the memory-impaired group.

Synaptogenesis refers to the growth and upkeep of the connections between neurons. Synaptic modifications are crucial for memory formation, and a generalised disruption of this process appears to fit with the reported memory deficits. However, higher-powered studies and expansion to other brain regions would be needed to bolster these findings.

Bulk vs Single Nucleus RNA Seq: The Importance of Single Cell Methods

This study also demonstrates the importance of covering multiple bases when it comes to -omics methods in neuroscience. The authors conducted a previous study using bulk RNA sequencing of TLE patients with and without memory impairments, and found the opposite result—downregulation of implicated genes in the memory-impaired group. They speculate this is due to the bulk methods favouring the RNA of certain cell types over others, and therefore bulk methods may be less sensitive at detecting when a certain gene is unregulated in one cell type but downregulated in another. Reliance on one sequencing method may therefore produce inconsistent findings when performing exploratory profiling of neurological conditions.

Outsourcing Bioinformatics Analysis: How We Can Help

The applications of RNA-seq technologies are innumerable, and our clients are at the forefront of tackling these research questions with sophisticated bioinformatics approaches. However, choosing which methods to use and analyzing the resulting data is no small challenge.

As experts across data types from cutting-edge sequencing platforms, we can help you tackle the challenging computational tasks of storing, analyzing and interpreting genomic and transcriptomic data. Bridge Informatics’ bioinformaticians are trained bench biologists, so they understand the biological questions driving your computational analysis. Click here  to schedule a free introductory call with a member of our team.

Fionn O’Sullivan, Neuroscientist & Content Writer, Bridge Informatics

Fionn is a Content Writer at Bridge Informatics, a professional services firm that helps biotech customers implement advanced techniques in management and analysis of genomic data. Bridge Informatics focuses on data mining, machine learning, and various bioinformatic techniques to discover biomarkers and companion diagnostics. If you’re interested in reaching out, please email daniel.dacey@old.bridgeinformatics.com or dan.ryder@old.bridgeinformatics.com.

Recent Posts