Hippocampal sclerosis is characterized by the loss of specific neuronal populations and exacerbated activation of other cell types resident in the brain, such as microglia and astrocytes. However, understanding why some neuronal types are more vulnerable than others has remained largely unclear.

In this work, the researchers have developed a transcriptional map that identifies the precise genetic code of all cell types specifically affected in the disease. With these maps we seek to match different genes with specific biological elements. In the case of the brain, we aim linking expression of some specific genes with different cell types, such as neurons, astrocytes and microglia. To do this, researchers applied two advanced procedures for biological sampling: Laser micro-dissection of localized brain tissue and sorting of individual cell nuclei extracted from rats and mice. Using cutting-edge genomic and bioinformatic approaches allowed them to identify specific genetic signatures of degenerative processes.

When neurons begin to degenerate, they release some signals that can be detected by microglia, which are mediating the inflammatory and neurotoxic response. Each of these processes involve the activation or inactivation of some genetic programs defining a specific genetic signature. We identify some of these genetic signatures associated to neuronal types. Researchers also recorded the electrical activity of individual neurons in vivo and found signs of epileptiform activities in some of them. These more hyperexcitable neurons tended to be located in a specific sublayer within the hippocampal region (the superficial sublayer) and expressed some characteristic genes. Very strikingly, we found that the hyperexcitability map perfectly matched neurodegeneration signatures.

To ease dissemination amongst the neuroscience and clinical communities, researchers have made the data associated with this study accessible as a public resource though two interactive websites.

Regards

John
Editorial Assistant
Immunogenetics Open Access