Ketogenic diet change cPLA2/clusterin and autophagy related gene expression and correlate with cognitive deficits and hippocampal MFs sprouting following neonatal seizures

Hóng, Ní; Zhao, Dongjing; Tian, Tian

doi:10.1016/j.eplepsyres.2015.11.021

Cited by 28 publications

(24 citation statements)

References 35 publications

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“…Knockout of ATG-7, a key molecule in the autophagy cascade, leads to spontaneous seizures in mice, implying that inhibition of autophagy is sufficient to induce epilepsy ( Boya et al, 2013 ). We also reported that ratio of LC3 II/I was downregulated in the hippocampus of newborn rats subjected to repeated seizure induction using flurothyl, indicating reduced numbers of autophagosomes, while p62 was upregulated, indicating enhanced autophagic flux ( Ni et al, 2016 ). Centromere protein V (CENPV) contributes to the maintenance of cell dynamics by stabilizing microtubules ( Honda et al, 2009 ), and this process is critical for autophagy.…”

Section: Discussionmentioning

confidence: 86%

“…After vehicle treatment or status epilepticus induction, Ctr and SE groups continued to receive a normal diet for 28 days (4.5% fat, 20% protein and 50% carbohydrate), while the SE + KD group was fed the KD for 28 days (70% fat, 20% protein, and no carbohydrate). The KD formula was reported in detail previously ( Ni et al, 2016 ). Further detail contents of the diets are shown in Table 1 .…”

Section: Methodsmentioning

confidence: 99%

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Proteomics for Studying the Effects of Ketogenic Diet Against Lithium Chloride/Pilocarpine Induced Epilepsy in Rats

et al. 2020

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The ketogenic diet (KD) demonstrates antiepileptogenic and neuroprotective efficacy, but the precise mechanisms are unclear. Here we explored the mechanism through systematic proteomics analysis of the lithium chloride-pilocarpine rat model. Sprague-Dawley rats (postnatal day 21, P21) were randomly divided into control (Ctr), seizure (SE), and KD treatment after seizure (SE + KD) groups. Tandem mass tag (TMT) labeling and liquid chromatography-tandem mass spectroscopy (LC-MS/MS) were utilized to assess changes in protein abundance in the hippocampus. A total of 5,564 proteins were identified, of which 110 showed a significant change in abundance between the SE and Ctr groups (18 upregulated and 92 downregulated), 278 between SE + KD and SE groups (218 upregulated and 60 downregulated), and 180 between Ctr and SE + KD groups (121 upregulated and 59 downregulated) (all p < 0.05). Seventy-nine proteins showing a significant change in abundance between SE and Ctr groups were reciprocally regulated in the SD + KD group compared to the SE group (i.e., the seizure-induced change was reversed by KD). Of these, five (dystrobrevin, centromere protein V, oxysterol-binding protein, tetraspanin-2, and progesterone receptor membrane component 2) were verified by parallel reaction monitoring. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis indicated that proteins of the synaptic vesicle cycle pathway were enriched both among proteins differing in abundance between SE and Ctr groups as well as between SE + KD and SE groups. This comprehensive proteomics analyze of KD-treated epilepsy by quantitative proteomics revealed novel molecular mechanisms of KD antiepileptogenic efficacy and potential treatment targets.

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Section: Discussionmentioning

confidence: 86%

Section: Methodsmentioning

confidence: 99%

Proteomics for Studying the Effects of Ketogenic Diet Against Lithium Chloride/Pilocarpine Induced Epilepsy in Rats

et al. 2020

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“…Animals were randomly assigned to two groups: the flurothyl (bis-2, 2, 2-triflurothyl ether; Sigma-Aldrich Chemical, WI, USA)-induced recurrent seizures group ( n = 20) and the control group ( n = 20). From P6 to P12, seizures were induced with flurothyl for 30 min per day for consecutive 7 days in recurrent seizures group ( 20 ), with a flow rate of 100 μl/min onto filter paper in the center of the container where it evaporated ( 21 ). Flurothyl (bis-2,2,2-triflurothyl ether) is an inhaled anesthetic that induces generalized tonic-clonic seizures in the central nervous system, which is effective and rapid acting.…”

Section: Methodsmentioning

confidence: 99%

“…After the anesthesia, the rats in each group were perfused through cardioplegia in the order of 0.9% normal saline (80 ml), 4% paraformaldehyde PB solution (100 ml), 0.4% sodium sulfide (80 ml) and 4% paraformaldehyde PB solution (60 ml). The method of Timm staining ( n = 5/each group, P34) has been described previously ( 20 ). Arabic gum powder (45 g) was dissolved in 90 ml of double distilled water.…”

Section: Methodsmentioning

confidence: 99%

“…The results suggested that zinc-induced lipid peroxidation and mitochondrial metabolic pathway may be the therapeutic target of KD ( 19 ). Chronic KD treatment restored the up-regulated clusterin and autophagy-related genes Beclin-1, p62 and Cathepsin-E following neonatal seizure, indicating that the autophagy signaling may be involved in the zinc/mitochondrial metabolic pathway ( 20 ).…”

Section: Introductionmentioning

confidence: 99%

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Zinc/CaMK II Associated-Mitophagy Signaling Contributed to Hippocampal Mossy Fiber Sprouting and Cognitive Deficits Following Neonatal Seizures and Its Regulation by Chronic Leptin Treatment

Jin

Hóng

2018

Front. Neurol.

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The role of leptin in the pathogenesis of epilepsy is getting more and more attention in clinical and basic research. Although there are data indicating neuroprotective effects of elevated serum/brain leptin levels following acute seizures, no study to date has dealt with the impact of chronic leptin treatment on long-term brain injury following developmental seizures. The aim of this study was to evaluate whether chronic leptin treatment may have neuroprotective effects on cognitive and hippocampal mossy fiber sprouting following flurothyl-induced recurrent neonatal seizures and whether these effects are mediated by the zinc/CaMKII-associated mitophagy signaling pathway. Forty Sprague-Dawley rats (postnatal day 6, P6) were randomly assigned into two groups: neonatal seizure group and control group. At P13, they were further divided into control group, seizure group (RS), control + leptin (leptin, i.p., 2 mg/kg/day for 10 days), seizure+leptin group (RS+Leptin, 2mg/kg/day, i.p., for 10 consecutive days). Morris water maze test was performed during P27-P32. Subsequently, Timm staining and Western blotting were used to detect the mossy fiber sprouting and protein levels in hippocampus. Flurothyl-induced seizures (RS group) significantly down-regulated mitophagy markers PINK, Drp1, PHB, and memory marker CaMK II alpha while up-regulating zinc transporters ZnT3, ZnT4, ZIP7, and autophagy execution molecular cathepsin-E, which were paralleled with hippocampal aberrant mossy fiber sprouting and cognitive dysfunction. However, these changes were restored by chronic leptin treatment (RS+Leptin group). The results showed that leptin had neuroprotective effect on hippocampal pathological damage and cognitive deficits induced by neonatal seizures and suggested that Zinc/CaMK II associated-mitophagy signaling pathway in hippocampus may be a new target of leptin's neuroprotection, with potential value of translational medicine.

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Potential of Capric Acid in Neurological Disorders: An Overview

et al. 2022

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Ketogenic diet change cPLA2/clusterin and autophagy related gene expression and correlate with cognitive deficits and hippocampal MFs sprouting following neonatal seizures

Cited by 28 publications

References 35 publications

Proteomics for Studying the Effects of Ketogenic Diet Against Lithium Chloride/Pilocarpine Induced Epilepsy in Rats

Proteomics for Studying the Effects of Ketogenic Diet Against Lithium Chloride/Pilocarpine Induced Epilepsy in Rats

Zinc/CaMK II Associated-Mitophagy Signaling Contributed to Hippocampal Mossy Fiber Sprouting and Cognitive Deficits Following Neonatal Seizures and Its Regulation by Chronic Leptin Treatment

Potential of Capric Acid in Neurological Disorders: An Overview

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