Altered adult neurogenesis and gliogenesis in patients with mesial temporal lobe epilepsy.

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Publication Year:
2022
Authors:
Aswathy Ammothumkandy, Kristine Ravina, Victoria Wolseley, Alexandria N Tartt, Pen-Ning Yu, Luis Corona, Naibo Zhang, George Nune, Laura Kalayjian, J John Mann, Gorazd B Rosoklija, Victoria Arango, Andrew J Dwork, Brian Lee, J A D Smith, Dong Song, Theodore W Berger, Christianne Heck, Robert H Chow, Maura Boldrini, Charles Y Liu, Jonathan J Russin, Michael A Bonaguidi
PubMed ID:
35383330
Funding Grants:
Public Summary:
Epilepsy often involves abnormal brain activity in the hippocampus. In humans with mesial temporal lobe epilepsy (MTLE), prolonged epilepsy reduces the creation of new neurons while immature astroglial cells remain constant. These newly formed neurons are often inactive and absent during epileptic activity. In contrast, immature astroglial cells are consistently present and linked to epileptic activity. This research suggests that targeting immature astroglial cells may be a way to control excessive brain activity in people with epilepsy.
Scientific Abstract:
The hippocampus is the most common seizure focus in people. In the hippocampus, aberrant neurogenesis plays a critical role in the initiation and progression of epilepsy in rodent models, but it is unknown whether this also holds true in humans. To address this question, we used immunofluorescence on control healthy hippocampus and surgical resections from mesial temporal lobe epilepsy (MTLE), plus neural stem-cell cultures and multi-electrode recordings of ex vivo hippocampal slices. We found that a longer duration of epilepsy is associated with a sharp decline in neuronal production and persistent numbers in astrogenesis. Further, immature neurons in MTLE are mostly inactive, and are not observed in cases with local epileptiform-like activity. However, immature astroglia are present in every MTLE case and their location and activity are dependent on epileptiform-like activity. Immature astroglia, rather than newborn neurons, therefore represent a potential target to continually modulate adult human neuronal hyperactivity.