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

• Published in: Molecular neurobiology Vol. 61; no. 8; pp. 5601 - 5613
• Main Authors: Yu, Xiu, Yang, Han, Lv, HongJie, Lu, Haimei, Zhao, Huawei, Xu, Zhenghao
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.08.2024; Springer Nature B.V
• Subjects: Age groups; Aging; Biomedical and Life Sciences; Biomedicine; Brain-derived neurotrophic factor; Cell Biology; Comorbidity; Convulsions & seizures; Cornea; Drug resistance; Epilepsy; Etiracetam; Eye diseases; Gliosis; Hippocampus; Hyperactivity; Kindling; Lamotrigine; Middle age; Neurobiology; Neurology; Neurosciences; Phenytoin; Seizures; Valproic acid; Cognitive and psychiatric comorbidities; Pharmacoresistance; Antiseizure medications; BDNF-ERK signaling; Epilepsy
• ISSN: 0893-7648; 1559-1182; 1559-1182
• DOI: 10.1007/s12035-024-03934-x

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.