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Volume 14
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10.3390/cells14040281
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Article

Imipramine, an Acid Sphingomyelinase Inhibitor, Promotes Newborn Neuron Survival in the Hippocampus After Seizure

by
Song Hee Lee
1,†,
Hyun Wook Yang
1,†,
Beom Seok Kang
1,
Min Kyu Park
1,
Dong Yeon Kim
1,
Hong Ki Song
2,
Hui Chul Choi
3,
Minwoo Lee
4,
Bo Young Choi
5,
Dae-Soon Son
6 and
Sang Won Suh
1,7,*
1
Department of Physiology, College of Medicine, Hallym University, Chuncheon 24252, Republic of Korea
2
Department of Neurology, Kangdong Sacred Heart Hospital, Seoul 05355, Republic of Korea
3
Department of Neurology, Hallym University Sacred Heart Hospital, Chuncheon 24253, Republic of Korea
4
Department of Neurology, Hallym University Sacred Heart Hospital, Anyang 14068, Republic of Korea
5
Department of Physical Education, Hallym University, Chuncheon 24253, Republic of Korea
6
Division of Data Science, Data Science Convergence Research Center, Hallym University, Chuncheon 24253, Republic of Korea
7
Hallym Institute of Epilepsy Research, Chuncheon 24253, Republic of Korea
*
Author to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Cells 2025, 14(4), 281; https://doi.org/10.3390/cells14040281
Submission received: 7 January 2025 / Revised: 11 February 2025 / Accepted: 11 February 2025 / Published: 14 February 2025
(This article belongs to the Special Issue Advances in Neurogenesis: 3rd Edition)
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Abstract

Epilepsy, a chronic neurological disorder, is triggered by various insults, including traumatic brain injury and stroke. Acid sphingomyelinase (ASMase), an enzyme that hydrolyzes sphingomyelin into ceramides, is implicated in oxidative stress, neuroinflammation, and neuronal apoptosis. Ceramides, which have pro-apoptotic properties, contribute to oxidative damage and lysosomal dysfunction, exacerbating neuronal injury. This study investigates the role of ASMase in epilepsy, hypothesizing that seizure activity upregulates ASMase, increasing ceramide levels, DNA damage, and neuronal apoptosis. We employed a pilocarpine-induced rat seizure model and examined the effects of imipramine, an ASMase inhibitor, administered intraperitoneally (10 mg/kg) for four weeks post-seizure induction. Histological and cognitive analyses showed that while imipramine did not prevent early neuronal death within the first week, it significantly reduced markers of neuronal apoptosis by four weeks. Imipramine also promoted hippocampal neurogenesis and preserved cognitive function, which is often impaired following seizures. These findings suggest that ASMase inhibition could mitigate neuronal apoptosis and improve cognitive recovery after seizures. Imipramine may serve as a promising therapeutic strategy for epilepsy-associated neuronal damage and cognitive deficits. Further studies should delineate the molecular mechanisms of ASMase inhibition and evaluate its long-term efficacy in addressing epilepsy-related neurodegeneration and functional impairments.
Keywords: epilepsy; imipramine; ceramide; acid sphingomyelinase; neuron death; neurogenesis; cognitive function epilepsy; imipramine; ceramide; acid sphingomyelinase; neuron death; neurogenesis; cognitive function
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MDPI and ACS Style

Lee, S.H.; Yang, H.W.; Kang, B.S.; Park, M.K.; Kim, D.Y.; Song, H.K.; Choi, H.C.; Lee, M.; Choi, B.Y.; Son, D.-S.; et al. Imipramine, an Acid Sphingomyelinase Inhibitor, Promotes Newborn Neuron Survival in the Hippocampus After Seizure. Cells 2025, 14, 281. https://doi.org/10.3390/cells14040281

AMA Style

Lee SH, Yang HW, Kang BS, Park MK, Kim DY, Song HK, Choi HC, Lee M, Choi BY, Son D-S, et al. Imipramine, an Acid Sphingomyelinase Inhibitor, Promotes Newborn Neuron Survival in the Hippocampus After Seizure. Cells. 2025; 14(4):281. https://doi.org/10.3390/cells14040281

Chicago/Turabian Style

Lee, Song Hee, Hyun Wook Yang, Beom Seok Kang, Min Kyu Park, Dong Yeon Kim, Hong Ki Song, Hui Chul Choi, Minwoo Lee, Bo Young Choi, Dae-Soon Son, and et al. 2025. "Imipramine, an Acid Sphingomyelinase Inhibitor, Promotes Newborn Neuron Survival in the Hippocampus After Seizure" Cells 14, no. 4: 281. https://doi.org/10.3390/cells14040281

APA Style

Lee, S. H., Yang, H. W., Kang, B. S., Park, M. K., Kim, D. Y., Song, H. K., Choi, H. C., Lee, M., Choi, B. Y., Son, D.-S., & Suh, S. W. (2025). Imipramine, an Acid Sphingomyelinase Inhibitor, Promotes Newborn Neuron Survival in the Hippocampus After Seizure. Cells, 14(4), 281. https://doi.org/10.3390/cells14040281

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