Role of Immature Neurons and Astroglia in Modulating Neuronal Hyperactivity and Cognition in Human Epilepsy Patients
Abstract number :
3.053
Submission category :
1. Basic Mechanisms / 1D. Mechanisms of Therapeutic Interventions
Year :
2024
Submission ID :
785
Source :
www.aesnet.org
Presentation date :
12/9/2024 12:00:00 AM
Published date :
Authors :
Presenting Author: Aswathy Ammothumkandy, PhD – University of Southern California
Kristine Ravina, MD PhD – University of Southern California
Victoria Wolseley, MS – University of Southern California
Alexandria N Tartt, MS – Columbia University
Pen-Ning Yu, PhD – University of Southern California
Luis Corona, MS – University of Southern California
Nadiya Atai, MD PhD – University of Southern California
Aidin Abedi, MD – University of Southern California
Lina M. D’Orazio, PhD – University of Southern California
Jeremy Nelson, MS – University of Southern California
Virginia Zuverza-Chavarria, PhD – University of Southern California
Alisha Cayce, – University of Southern California
Shariq Mohammad, PhD – University of Southern California
George Nune, MD – University of Southern California
Laura Kalayjian, MD – University of Southern California
Brian Lee, MD, PhD, FAANS – Keck School of Medicine, University of Southern California
Dong Song, PhD – University of Southern California
Theodore W Berger, PhD – University of Southern California
Christianne Heck, MD, MMM, FAES – University of Southern California
Robert H Chow, PhD – University of Southern California
Maura Boldrini, PhD – Columbia University
Charles Liu, MD, PhD – Keck School of Medicine, University of Southern California
Jason A D Smith, PhD – UT Southwestern Medical Center
Jonathan J Russin, MD – University of Southern California
Michael A Bonaguidi, PhD – University of Southern california
Rationale: Aberrant neuronal activity is a defining feature of epilepsy, leading to debilitating seizures and progressive cognitive decline. Mesial Temporal Lobe Epilepsy (MTLE) is the most common drug resistant form of adult epilepsy, attributed to abnormal local firing in the hippocampus. Within the hippocampus, aberrant cell genesis plays a critical role in the initiation and progression of epilepsy in rodent models; but it’s role in human epilepsy is still unclear. In this study we investigate the role of newborn immature neurons and astroglia towards neuronal hyperactivity and cognitive decline in human MTLE patients.
Methods: Pharmacoresistant MTLE patients undergo resective surgery to prevent further seizures. Surgical resections from epilepsy patients provide a unique window to investigate mechanisms driving the disease, which can define new targets for drug resistant epilepsies. We used a combination of histology, neural stem cell cultures and multi-electrode array recordings on surgical resections from MTLE patients and further integrated it with clinical and neuropsychological assessment to study how immature neurons and astroglia are linked to neuronal hyperactivity and cognitive decline.
Results: Our study revealed that neurogenesis declined with increasing disease duration, neuronal hyperactivity, and associated with verbal learning impairment in human MTLE patients. In addition to neurogenesis, we observed pathological immature astrocytes that are persistently present during epilepsy progression whose activity anticorrelated with neuronal hyperactivity. We further observed an age-related increase in Dcx+ immature astroglia, which is linked with a decline in intelligence and reasoning.
Conclusions: In summary, our study offers foundational evidence supporting immature neurons and astroglia as potential therapeutic targets for mitigating neuronal hyperactivity and cognitive decline in individuals with epilepsy.
Funding: This work was supported by the NIH (R56AG064077, R01AG076956 to M.A.B; U01MH098937 to R.H.C), Donald E. and Delia B. Baxter Foundation, L.K. Whittier Foundation, Eli and Edythe Broad Foundation (to M.A.B and J.J.R), USC Neurorestoration Center (to J.J.R and C.Y.L.), Rudi Schulte Research Institute (to C.Y.L.), American Epilepsy Society (to A.AK) and California Institute of Regenerative medicine (to A.AK).
Basic Mechanisms