11β-HSD1 participates in epileptogenesis and the associated cognitive impairment by inhibiting apoptosis in mice

Background Glucocorticoid signalling is closely related to both epilepsy and associated cognitive impairment, possibly through mechanisms involving neuronal apoptosis. As a critical enzyme for glucocorticoid action, the role of 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1) in epileptogenesis and ass...

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Published in:Journal of translational medicine 2022-09, Vol.20 (1), p.1-406, Article 406
Main Authors: Li, Xueying, Qiu, Wanhua, Deng, Lu, Lin, Jingjing, Huang, Wenting, Xu, Yuchen, Zhang, Mulan, Jones, Nigel C., Lin, Runxuan, Xu, Huiqin, Lin, Li, Li, Peijun, Wang, Xinshi
Format: Article
Language:English
Subjects:
11β-Hydroxysteroid dehydrogenase
11β-hydroxysteroid dehydrogenase 1 (11β-HSD1)
Action potential
Alzheimer's disease
Animal cognition
Apoptosis
Astrocytes
Bcl-2 protein
Caspase-3
Cognitive ability
Cognitive impairment
Comorbidity
Convulsions & seizures
Dehydrogenases
Epilepsy
Excitability
Firing rate
Glucocorticoids
Hippocampus
Hormones
Kindling
Laboratory animals
Latent period
Medical research
Memory
Neurons
Patch clamp
Pentylenetetrazole
Seizures
Spatial discrimination learning
Spatial memory
Stress
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Summary:Background Glucocorticoid signalling is closely related to both epilepsy and associated cognitive impairment, possibly through mechanisms involving neuronal apoptosis. As a critical enzyme for glucocorticoid action, the role of 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1) in epileptogenesis and associated cognitive impairment has not previously been studied. Methods We first investigated the expression of 11β-HSD1 in the pentylenetetrazole (PTZ) kindling mouse model of epilepsy. We then observed the effect of overexpressing 11β-HSD1 on the excitability of primary cultured neurons in vitro using whole-cell patch clamp recordings. Further, we assessed the effects of adeno-associated virus (AAV)-induced hippocampal 11β-HSD1 knockdown in the PTZ model, conducting behavioural observations of seizures, assessment of spatial learning and memory using the Morris water maze, and biochemical and histopathological analyses. Results We found that 11β-HSD1 was primarily expressed in neurons but not astrocytes, and its expression was significantly (p 
ISSN:1479-5876
1479-5876
DOI:10.1186/s12967-022-03618-x