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Age-Dependent Phenomena of 6-Hz Corneal Kindling Model in Mice

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Abstract

Although numerous studies have acknowledged disparities in epilepsy-related disease processes between young and aged animals, little is known about how epilepsy changes from young adulthood to middle age. This study investigates the impact of aging on 6-Hz corneal kindling in young-adult mice and middle-aged mice. We found that the kindling acquisition of the 6-Hz corneal kindling model was delayed in middle-aged mice when compared to young-adult mice. While the seizure stage and incidence of generalized seizures (GS) were similar between the two age groups, the duration of GS in the kindled middle-aged mice was shorter than that in the kindled young-adult mice. Besides, all kindled mice, regardless of age, were resistant to phenytoin sodium (PHT), valproate sodium (VPA), and lamotrigine (LGT), whereas middle-aged mice exhibited higher levetiracetam (LEV) resistance compared to young-adult mice. Both age groups of kindled mice displayed hyperactivity and impaired memory, which are common behavioral characteristics associated with epilepsy. Furthermore, middle-aged mice displayed more pronounced astrogliosis in the hippocampus. Additionally, the expression of Brain-Derived Neurotrophic Factor (BDNF) was lower in middle-aged mice than in young-adult mice prior to kindling. These data demonstrate that both the acquisition and expression of 6-Hz corneal kindling are attenuated in middle-aged mice, while hippocampal astrogliosis and pharmacological resistance are more pronounced in this age group. These results underscore the importance of considering age-related factors when utilizing the 6-Hz corneal kindling model in mice of varying age groups.

Highlights

Middle-aged mice showed delayed corneal kindling and milder kindled seizure.

Kindled middle-aged mice showed an increased drug resistance to levetiracetam.

Kindling induced similar cognitive and psychiatric comorbidities in both groups.

Kindled middle-aged mice displayed more pronounced astrogliosis in the hippocampus.

Hippocampal BDNF levels were lower in middle-aged mice before kindling.

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Data Availability

The authors confirm that the data supporting the findings of this study are available within the article or its supplementary materials. The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

This work was supported by The Natural Science Foundation of Zhejiang, (Grant/Award Number: LY22H280007 and LYY22H310002); The National Natural Science Foundation of China, (Grant/Award Number: 82174005 and 82003720); Special Fund for the Incubation of Young Clinical Scientist, The Children’s Hospital of Zhejiang University School of Medicine, (Grant/Award Number: CHZJU2023YS006).

Funding

The Natural Science Foundation of Zhejiang, Grant/ Award Number: LY22H280007 and LYY22H310002; The National Natural Science Foundation of China, Grant/ Award Number: 82174005 and 82003720. Special Fund for the Incubation of Young Clinical Scientist, The Children’s Hospital of Zhejiang University School of Medicine, (Grant/Award Number: CHZJU2023YS006).

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  1. Xiu Yu, Han Yang and HongJie Lv contributed equally to this work.

Authors and Affiliations

  1. Laboratory of Rheumatology & Institute of TCM Clinical Basic Medicine, College of Basic Medical Science, Zhejiang Chinese Medical University, No.548 Binwen Road, Hangzhou, Zhejiang, 310053, China

    Xiu Yu, Han Yang, HongJie Lv, Haimei Lu & Zhenghao Xu

  2. Key Laboratory of Chinese Medicine Rheumatology of Zhejiang Province, College of Basic Medical Science, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China

    Xiu Yu, Han Yang, HongJie Lv, Haimei Lu & Zhenghao Xu

  3. Department of Pharmacy, The Children’s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, China

    Huawei Zhao

  4. Key Laboratory of Neuropharmacology and Translational Medicine of Zhejiang Province, College of Basic Medical Science, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China

    Zhenghao Xu

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Contributions

Z-HX and H-WZ designed the study. X.Y did the experimental validation. H.Y, H-ML and H-JL helped to check data and do the subgroup analyses. Z-HX and X.Y. wrote the manuscript.

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Correspondence to Huawei Zhao or Zhenghao Xu.

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Yu, X., Yang, H., Lv, H. et al. Age-Dependent Phenomena of 6-Hz Corneal Kindling Model in Mice. Mol Neurobiol (2024). https://doi.org/10.1007/s12035-024-03934-x

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