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. analyzed cortical tissue samples from 6 patients with TLE, comparing those patients with and without memory deficits. Using machine learning to identify enriched signaling 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 generalized 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 favoring 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.
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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 the 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 [email protected] or [email protected].