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This study was funded by the Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP): 2016/23509-4 and 2018/10089-2 (LA), 2014/03989-6 and 2019/00849-2 (RS-J), and 2015/22327-7 (AC). CD received scholarships from Coordenacao de Aperfeicoamento de Pessoal deNivel Superior (CAPES, Brazil, code 001), LA and NG-C has a CNPq Research Fellowship.

Analysis of institutional authors

Patricio Da Silva Junior, Rui MiltonAuthor

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February 9, 2024
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Energy Metabolism and Redox State in Brains of Wistar Audiogenic Rats, a Genetic Model of Epilepsy

Publicated to:Frontiers In Neurology. 10 1007- - 2019-10-01 10(), DOI: 10.3389/fneur.2019.01007

Authors: Porto Dechandt, Carlos Roberto; Ferrari, Gustavo Duarte; dos Santos, Jonathas Rodrigo; Cortes de Oliveira, Jose Antonio; Patricio Silva-Jr, Rui Milton; Siqueira Cunha, Alexandra Olimpio; Garcia-Cairasco, Norberto; Alberici, Luciane Carla

Affiliations

Univ Sao Paulo, Fac Ciencias Farmaceut Ribeirao Preto, Dept Fis & Quim, Ribeirao Preto, Brazil - Author
Univ Sao Paulo, Fac Med Ribeirao Preto, Dept Fisiol, Ribeirao Preto, Brazil - Author

Abstract

The Wistar Audiogenic Rat (WAR) strain is a genetic model of epilepsy, specifically brainstem-dependent tonic-clonic seizures, triggered by acute auditory stimulation. Chronic audiogenic seizures (audiogenic kindling) mimic temporal lobe epilepsy, with significant participation of the hippocampus, amygdala, and cortex. The objective of the present study was to characterize the mitochondrial energy metabolism in hippocampus and cortex of WAR and verify its relationship with seizure severity. Hippocampus of WAR naive (no seizures) presented higher oxygen consumption in respiratory states related to the maximum capacities of phosphorylation and electron transfer system, elevated mitochondrial density, lower GSH/GSSG and catalase activity, and higher protein carbonyl and lactate contents, compared with their Wistar counterparts. Audiogenic kindling had no adding functional effect in WAR, but in Wistar, it induced the same alterations observed in the audiogenic strain. In the cortex, WAR naive presented elevated mitochondrial density, lower GSH/GSSG and catalase activity, and higher protein carbonyl levels. Chronic acoustic stimulation in Wistar induced the same alterations in cortex and hippocampus. Mainly in the hippocampus, WAR naive presented elevated mRNA expression of glucose, lactate and excitatory amino acids transporters, several glycolytic enzymes, lactate dehydrogenase, and Na+/K+ ATPase in neurons and in astrocytes. In vivo treatment with mitochondrial uncoupler 2,4-dinitrophenol (DNP) or N-acetylcysteine (NAC) in WAR had no effect on mitochondrial metabolism, but lowered oxidative stress. Unlike DNP, NAC downregulated all enzyme genes involved in glucose and lactate uptake, and metabolism in neurons and astrocytes. Additionally, it was able to reduce brainstem seizure severity in WAR. In conclusion, in WAR naive animals, both cerebral cortex and hippocampus display elevated mitochondrial density and/or activity associated with oxidative damage, glucose and lactate metabolism pathways upregulation, and increased Na+/K+ ATPase mRNA expression. Only in vivo treatment with NAC was able to reduce seizure severity of kindled WARs, possibly via down regulation of glucose/lactate metabolism. Taken together, our results are a clear contribution to the field of mitochondrial metabolism associated to epileptic seizures.

Keywords

2,4-dinitrophenol (dnp)audiogenic kindlingexpressionglutathione-peroxidaseglycolysishippocampushuman-cellsliver-mitochondrian-acetylcysteinen-acetylcysteine (nac)na+/k+ atpasereactive oxygen speciesseizuressuperior-colliculuswar strainwistar audiogenic rats (war)MitochondriaOxidative stress

Quality index

Bibliometric impact. Analysis of the contribution and dissemination channel

The work has been published in the journal Frontiers In Neurology due to its progression and the good impact it has achieved in recent years, according to the agency WoS (JCR), it has become a reference in its field. In the year of publication of the work, 2019, it was in position 92/204, thus managing to position itself as a Q2 (Segundo Cuartil), in the category Clinical Neurology. Notably, the journal is positioned en el Cuartil Q2 para la agencia Scopus (SJR) en la categoría Neurology (Clinical).

From a relative perspective, and based on the normalized impact indicator calculated from the Field Citation Ratio (FCR) of the Dimensions source, it yields a value of: 2.23, which indicates that, compared to works in the same discipline and in the same year of publication, it ranks as a work cited above average. (source consulted: Dimensions Jul 2025)

Specifically, and according to different indexing agencies, this work has accumulated citations as of 2025-07-07, the following number of citations:

  • WoS: 12

Impact and social visibility

From the perspective of influence or social adoption, and based on metrics associated with mentions and interactions provided by agencies specializing in calculating the so-called "Alternative or Social Metrics," we can highlight as of 2025-07-07:

  • The use, from an academic perspective evidenced by the Altmetric agency indicator referring to aggregations made by the personal bibliographic manager Mendeley, gives us a total of: 39.
  • The use of this contribution in bookmarks, code forks, additions to favorite lists for recurrent reading, as well as general views, indicates that someone is using the publication as a basis for their current work. This may be a notable indicator of future more formal and academic citations. This claim is supported by the result of the "Capture" indicator, which yields a total of: 39 (PlumX).

With a more dissemination-oriented intent and targeting more general audiences, we can observe other more global scores such as:

  • The Total Score from Altmetric: 10.25.
  • The number of mentions on the social network X (formerly Twitter): 2 (Altmetric).
  • The number of mentions in news outlets: 1 (Altmetric).

It is essential to present evidence supporting full alignment with institutional principles and guidelines on Open Science and the Conservation and Dissemination of Intellectual Heritage. A clear example of this is:

  • The work has been submitted to a journal whose editorial policy allows open Open Access publication.

Leadership analysis of institutional authors

This work has been carried out with international collaboration, specifically with researchers from: Brazil.