Altered Adult Neurogenesis and Gliogenesis in Mesial Temporal Lobe Epilepsy Patients
Abstract number :
3.003
Submission category :
1. Basic Mechanisms / 1A. Epileptogenesis of acquired epilepsies
Year :
2021
Submission ID :
1825545
Source :
www.aesnet.org
Presentation date :
12/6/2021 12:00:00 PM
Published date :
Nov 22, 2021, 06:44 AM
Authors :
Aswathy Ammothumkandy, PhD - University of Southern California; Kristine Ravina, MD - University of Southern California; Victoria Wolseley, PhD student - University of Southern California; Alexandria Tartt, MD student - NYS Psychiatric Institute; Pen-Ning Yu, PhD - University of Southern California; Luis Corona, CIRM Undergraduate student - University of Southern California; Naibo Zhang, PhD student - University of Southern California; George Nune, MD - Keck school of Medicine; Laura Kalayjian, MD - Keck school of Medicine; John Mann, MD - Columbia University; Gorazd Rosoklija, MD, PhD - Columbia University; Victoria Arango, PhD - Columbia University; Andrew Dwork, MD - Columbia University; Brian Lee, MD - Keck school of Medicine; Jason Smith, PhD - Keck school of Medicine; Dong Song, PhD - University of Southern California; Theodore Berger, PhD - University of Southern California; Christianne Heck, MD - Keck school of Medicine; Robert Chow, MD, PhD - University of Southern California; Maura Boldrini, MD - Columbia University; Charles Liu, MD, PhD - Keck school of Medicine; Jonathan Russin, MD - Keck school of Medicine; Michael Bonaguidi, PhD - University of Southern California
Rationale: The hippocampus is the most common seizure focus in people. Within the hippocampus, aberrant neurogenesis plays a critical role in the initiation and progression of epilepsy in rodent models. However, it is unknown whether this also holds true in humans as adult neurogenesis has been recently contested. In this study we determine whether cell genesis occurs in adult human mesial temporal lobe epilepsy patients and is altered by epilepsy disease duration and neuronal hyperactivity.
Methods: We performed histology and neural stem cell cultures on en bloc hippocampus resections from human MTLE patients to investigate whether cell genesis is altered by epilepsy disease duration. Immunofluorescence on postmortem tissue from healthy age-matched subjects was performed as a control. Further, a sequential multi-electrode array recording and histology approach on ex vivo MTLE hippocampal slices was used to determine how cell genesis is altered with neuronal hyperactivity.
Results: Immature neurons are found in healthy control tissue. We reveal a sharp decline in neuronal production upon longer MTLE disease duration, but detected no such change in astrogenesis. Further, immature neurons in MTLE are mostly inactive, and are not observed in cases with local epileptiform activity. However, immature astroglia are present in every MTLE case and their location and activity are dependent upon epileptiform activity. The activity of immature glial cells anti-correlates with epileptiform activity within the dentate gyrus. These immature glia are not observed in control healthy tissue.
Conclusions: Our study finds that adult neurogenesis occurs in human epilepsy patients which declines upon MTLE disease duration and epileptiform activity in the dentate gyrus. This drop in neurogenesis might account for several cognitive impairments that increase in MTLE patients during disease progression. Instead, immature astroglia are prevalent in epilepsy cases throughout MTLE progression, not detected in age-matched healthy individuals, and show altered location and activity upon local epileptiform activity. These results point to a greater role for adult astrogenesis in modulating seizure activity.
Funding: Please list any funding that was received in support of this abstract.: Broad Innovation Grant, American Epilepsy Society Postdoctoral fellowship.
Basic Mechanisms