Vitamin D Pretreatment Modulates PINK1/Parkin-Related Mitophagy and Attenuates Seizure-Associated Brain Injury in Pentylenetetrazole- and Kainic acid -Induced Acute Epilepsy Models
W skrócie
[Preprint - wstępne wyniki] Badacze sprawdzili, czy podawanie witaminy D przed wywołaniem napadów epileptycznych zmniejsza ich natężenie i chroni mózg. W dwóch modelach ostrych napadów padaczkowych (u myszy) witamina D zmniejszyła częstość napadów, przedłużyła czas ich pojawienia się i ograniczyła uszkodzenia tkanki mózgowej w hipokampie. Efekt neuroprotektywny witaminy D wiązał się z normalizacją procesów czyszczenia uszkodzonych mitochondriów (zwanych mitofagią), szczególnie poprzez aktywację szlaków PINK1 i Parkina. Wyniki sugerują, że witamina D może chronić mózg przed padaczką poprzez poprawę zdolności komórek do usuwania wadliwych mitochondriów, choć potrzebne są dalsze badania.
Oryginalny abstract (angielski)
Abstract Objective To investigate whether vitamin D (VitD) pretreatment influences seizure outcomes and PINK1/Parkin-related mitophagy signalling in brain tissue using two acute epilepsy mouse models. Methods Acute seizure models were established using pentylenetetrazol (PTZ) or kainic acid (KA). Animals were allocated to control, model, VitD pretreatment, valproate (VPA) positive control, and VitD combined with the mitochondrial fission inhibitor Mdivi-1 groups. Seizure frequency, latency and severity were evaluated using behavioural observation and electroencephalography (EEG). Hippocampal neuronal injury and network remodelling were assessed by HE, Nissl and Timm staining, while mitochondrial ultrastructure and mitophagosome formation were examined by transmission electron microscopy (TEM). Expression of mitophagy-related markers (PINK1, Parkin, Drp1, p62 and LC3) was measured using qRT-PCR and western blotting. Results Both PTZ and KA induced epileptiform EEG activity, hippocampal neuronal injury, abnormal mossy fibre sprouting (MFS) and altered expression of mitophagy-related markers, accompanied by mitochondrial structural abnormalities. VitD pretreatment was associated with reduced seizure frequency, prolonged seizure latency and attenuation of hippocampal injury in both models. Molecular analyses showed altered expression of PINK1/Parkin pathway markers and partial normalisation of mitophagy-related proteins following VitD pretreatment. Combined intervention with Mdivi-1 was associated with additional modulation of mitochondrial dynamics-related markers and further improvement of histopathological and ultrastructural outcomes. Conclusions VitD pretreatment was associated with neuroprotective effects in acute PTZ- and KA-induced seizure models and modulation of PINK1/Parkin-related mitophagy signalling. These findings support a potential role of mitochondrial quality-control pathways in the biological effects of VitD under acute seizure conditions, while further mechanistic validation is required.
Metadane publikacji
Journal
Preprint (medRxiv/bioRxiv)
Data publikacji
04.05.2026
DOI
10.21203/rs.3.rs-9449541/v1
Europe PMC ID
PPR1184976
Autorzy
Liu J, Liu Y, Fu R, Fang L, Kong D, Wang L, Zeng P, Zhu X, Fu Y, Guo J