TY - JOUR
T1 - Altered adult neurogenesis and gliogenesis in patients with mesial temporal lobe epilepsy
AU - Ammothumkandy, Aswathy
AU - Ravina, Kristine
AU - Wolseley, Victoria
AU - Tartt, Alexandria N.
AU - Yu, Pen Ning
AU - Corona, Luis
AU - Zhang, Naibo
AU - Nune, George
AU - Kalayjian, Laura
AU - Mann, J. John
AU - Rosoklija, Gorazd B.
AU - Arango, Victoria
AU - Dwork, Andrew J.
AU - Lee, Brian
AU - Smith, J. A.D.
AU - Song, Dong
AU - Berger, Theodore W.
AU - Heck, Christianne
AU - Chow, Robert H.
AU - Boldrini, Maura
AU - Liu, Charles Y.
AU - Russin, Jonathan J.
AU - Bonaguidi, Michael A.
N1 - Funding Information:
We thank the families that gave consent for brain tissue collection and interviews to investigators at Columbia University, the New York State Psychiatric Institute and the University of Southern California. We thank teams performing the psychological autopsy interviews and M. J. Bakalian for assistance with laboratory equipment and software. We thank the USC Neurorestoration administration and clinical research staff for their support on this study. We thank A. P. McMahon and members of the Bonaguidi laboratory for helpful discussions.
Funding Information:
This work was supported by the National Institutes of Health (NIH) (R00NS089013, R56AG064077 to M.A.B.; MH83862, NS090415, MH94888 to M.B.; U01MH098937 to R.H.C.; MH64168, MH098786 to A.J.D.; MH40210 to V.A.; MH090964 to J.J.M.), the Donald E. and Delia B. Baxter Foundation, the L.K. Whittier Foundation, the Eli and Edythe Broad Foundation (to M.A.B.), the USC Neurorestoration Center (to J.J.R. and C.Y.L.), the Rudi Schulte Research Institute (to C.Y.L.), the American Foundation for Suicide Prevention SRG-0-129-12, the Brain and Behavior Research Foundation Independent Investigator Grant no. 56388, New York Stem Cell Initiative C029157 and C023054, the Dr Brigitt Rok-Potamkin’s Foundation, the Morris Stroud III Center for Study of Quality of Life in Health and Aging (to M.B.) and the American Epilepsy Society (to A.A.).
Publisher Copyright:
© 2022, The Author(s), under exclusive licence to Springer Nature America, Inc.
PY - 2022/4
Y1 - 2022/4
N2 - 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.
AB - 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.
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U2 - 10.1038/s41593-022-01044-2
DO - 10.1038/s41593-022-01044-2
M3 - Article
C2 - 35383330
AN - SCOPUS:85127696034
SN - 1097-6256
VL - 25
SP - 493
EP - 503
JO - Nature Neuroscience
JF - Nature Neuroscience
IS - 4
ER -