Depressive, inflammatory, and metabolic factors associated with cognitive impairment in patients with epilepsy

Arend, Josi; Kegler, Aline; Caprara, Ana Letícia Fornari; Almeida, Camila Danielle Aragão; Gabbi, Patrícia; Pascotini, Eduardo Tanuri; Freitas, Lori Ane Vargas de; Miraglia, Cinara; Bertazzo, Taíse Leitemperger; Palma, Raphael; Arceno, Patrícia; Duarte, Marta M.M.F.; Furian, Ana Flávia; Oliveira, Mauro Schneider; Royes, Luiz Fernando Freire; Mathern, Gary W.; Fighera, Michele Rechia

doi:10.1016/j.yebeh.2018.07.007

Cited by 31 publications

(14 citation statements)

References 50 publications

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“…Others have shortened life span due to the increased risk of unexpected sudden death that is associated with uncontrolled seizures [50][51][52]. Studies have shown that patients with epilepsy can be significant neuropsychological, psychiatric, and social impairments that limit employment, reduce marriage rates, and decrease quality of life [51][52][53]. Thus, genetic polymorphism becomes an "ally" to help discover the cause of drug refractoriness and provides insight into the type and magnitude of clinic-laboratorial manifestations may have across individuals, helping to determine the best treatment and improve the quality of life of patients with neurological diseases, such as epilepsy.…”

Section: Resultsmentioning

confidence: 99%

Apoptotic Markers Are Increased in Epilepsy Patients: A Relation with Manganese Superoxide Dismutase Ala16Val Polymorphism and Seizure Type through IL-1β and IL-6 Pathways

Kegler

Caprara

Pascotini

et al. 2020

BioMed Research International

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The MnSOD Ala16Val single nucleotide polymorphism (SNP) has been associated with different diseases. However, there are scarcely studies relating this SNP in epilepsy, a neurologic disease that involves some interacting pathways, such as apoptotic and inflammatory factors. In this sense, we decided to investigate the relationship of MnSOD Ala16Val SNP with apoptotic markers in epilepsy and its relation with inflammatory pathway and seizure type. Ninety subjects were evaluated (47 epilepsies; 43 controls) by questionnaires and laboratorial exams. We observed a higher percentage of VV genotype in the epilepsy group when compared to the control group. IL-1β, IL-6, caspase-1, and caspase-3 levels were increased in the epilepsy group (VV genotype). Furthermore, an important correlation between IL-1β vs. caspase-1 and IL-6 vs. caspase-3 was observed in the epilepsy group (VV genotype). The epilepsy group which presented generalized seizures also demonstrated a positive correlation between IL-1β vs. CASP1 and IL-6 vs. CASP3. Thus, it is a plausible propose that epilepsy patients with VV genotype and generalized seizures present a worse inflammatory and apoptotic status. Our findings suggest that the knowledge of MnSOD Ala16Val polymorphism existence is important to evaluate molecular mechanisms associated to seizure and improve the treatment of these patients.

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Section: Resultsmentioning

confidence: 99%

Apoptotic Markers Are Increased in Epilepsy Patients: A Relation with Manganese Superoxide Dismutase Ala16Val Polymorphism and Seizure Type through IL-1β and IL-6 Pathways

Kegler

Caprara

Pascotini

et al. 2020

BioMed Research International

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“…It was suggested to promote cell apoptosis and repress glycolipid metabolism pathway through inhibiting the expression of hexokinase 2 and ATP citrate lyase, the key enzymes related to glycolipid metabolism ( Dong et al, 2021 ). Given that the abnormal glycolipid metabolism was associated with cognitive dysfunction ( Arend et al, 2018 ; Qiu et al, 2022 ), the changes in the expression of mm9_circ_009789, mm9_circ_004229, Prkcb and Zbtb4 in our POCD model suggests that the PKC signaling pathway, neural cell apoptosis and glycolipid metabolism pathway may be regulated by mm9_circ_009789 and mm9_circ_004229-associated-ceRNA networks and involved in age-related POCD neuropathogenesis. Another target of mmu-miR-298-5P, Syngap1, was downregulated instead of upregulated in our POCD model, which may because it was powerfully affected by other ways of gene expression regulation rather than mmu-miR-298-5P.…”

Section: Discussionmentioning

confidence: 96%

Characterization of circRNA-Associated-ceRNA Networks Involved in the Pathogenesis of Postoperative Cognitive Dysfunction in Aging Mice

Zhang

Lin

Yang

et al. 2022

Front. Aging Neurosci.

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Postoperative cognitive dysfunction (POCD) is a clinical entity associated with declined cognitive function following surgery. It occurs more frequently in elderly patients. Recent studies have shown that circRNA-associated-ceRNA networks, constructed based on interactions between circRNA-miRNA and miRNA-mRNA, provide key insight into the molecular mechanisms underlying the pathogenesis of several neurological diseases. However, the mechanism of POCD remains undetermined. In this study, laparotomies were performed under isoflurane anesthesia on young (2-month-old) and aging (17-month-old) male C57BL/6 mice. The results showed that the aging mice were more likely than the young mice to develop POCD. Subsequently, differentially expressed circRNAs, miRNAs, and mRNAs were characterized by RNA sequencing the hippocampi of young and aging mice under control and surgery conditions. Six circRNAs, 6 miRNAs, and 203 mRNAs were identified to construct the circRNA-associated-ceRNA network for the control condition, while 13 circRNAs, 8 miRNAs, and 189 mRNAs were used for the circRNA-associated-ceRNA network for the surgery condition. Further Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of these two networks revealed that the circRNA-associated-ceRNA networks are involved in POCD pathogenesis though modulating the Wnt and VEGF signaling pathways, as well as neural processes associated with long-term synaptic depression and synaptic transmission. In particular, the mmu-miR-298-5P regulatory pathway identified in this study’s mouse model suggests that mm9_circ_009789- and mm9_circ_004229-associated-ceRNA networks as closely related to the occurrence of POCD through regulating PKC signaling pathway, neural cell apoptosis and glycolipid metabolism pathway. These findings provide possible insight into the role of the circRNA-associated-ceRNA networks, helping to unravel the complexity of the molecular pathogenesis of POCD.

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“…During seizures, various metabolites and metabolic pathways become dysregulated, such as changes in the abundance of essential products in the three acid cycles, energy metabolism, amino acid metabolism, phospholipid metabolism and purine metabolic pathways (9,10). At present, studies have found different metabolites in the cerebrospinal fluid of patients with epilepsy caused by traumatic brain injury, including glutamate, norepinephrine, homovanillic acid, hydroxyindole (8,11).…”

Section: Introductionmentioning

confidence: 99%

Metabonomic analysis of cerebrospinal fluid in epilepsy

et al. 2022

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Depressive, inflammatory, and metabolic factors associated with cognitive impairment in patients with epilepsy

Cited by 31 publications

References 50 publications

Apoptotic Markers Are Increased in Epilepsy Patients: A Relation with Manganese Superoxide Dismutase Ala16Val Polymorphism and Seizure Type through IL-1β and IL-6 Pathways

Apoptotic Markers Are Increased in Epilepsy Patients: A Relation with Manganese Superoxide Dismutase Ala16Val Polymorphism and Seizure Type through IL-1β and IL-6 Pathways

Characterization of circRNA-Associated-ceRNA Networks Involved in the Pathogenesis of Postoperative Cognitive Dysfunction in Aging Mice

Metabonomic analysis of cerebrospinal fluid in epilepsy

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