Gene Expression Analysis Identifies Cholesterol Metabolism Dysregulation in Hippocampus of Phenytoin-Resistant Pentylenetetrazol-Kindled Epileptic Mice

Abstract

Pharmaco-resistant Epilepsy has been a major challenge for medical interventions in controlling seizures. To date, up to 33% of the patients with epilepsy do not show adequate response to anti-epileptic drugs even after prolonged combinatorial drug usage. Using microarray, this study explores the changes in hippocampal gene expression in the phenytoin-resistant pentylenetetrazol (PTZ)-kindled mouse model of epilepsy. Our results from mRNA microarray analysis show distinct gene expression profiles in the hippocampus of phenytoin-resistant and sensitive mice. Pathway enrichment analysis showed differential expression of genes involved in cholesterol biosynthesis in phenytoin-resistant and sensitive mice.

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Data Availability

Microarray array data is being submitted to Geo data base and accession no would be provided here. Other data will be available on request.

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Acknowledgements

U. A. B. and N. K. acknowledge CSIR fellowship supports for doctoral research. Mr. Jedy Jose, CCMB, Animal House was duly acknowledged for his constant support in maintaining the quality of animals used for the study.

Funding

This research was jointly supported by the Council of Scientific and Industrial Research [BSC0103-UNDO to A. K. and S. C.] and Department of Biotechnology, India [BT/PR4014/MED/30/673/2011 to A. K.].

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SA and UAB contributed equally to this work. SA, AK, and UAB designed the biological experiments. SA UAB, MBM, SC performed the biological experiments. UAB and AK analyzed the array data. AK supervised all of the biological experiments. UAB, SA AK, NK and SC wrote the paper, and all authors reviewed and edited their part.

Corresponding authors

Correspondence to Sridhar Amalakanti or Arvind Kumar.

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There are no conflicts of interest among all authors.

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We confirm that we have read the journal’s position on issues involved in ethical publication and affirm that this report is consistent with those guidelines. Animal protocols were approved by Institutional Animal Ethics Committee (IAEC) of the CSIR- Centre for Cellular and Molecular Biology (CCMB), Hyderabad, India. The protocol was assigned the number #IAEC/CCMB/50/2018.

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Amalakanti, S., Bhat, U.A., Mylavarapu, M.B. et al. Gene Expression Analysis Identifies Cholesterol Metabolism Dysregulation in Hippocampus of Phenytoin-Resistant Pentylenetetrazol-Kindled Epileptic Mice. Neuromol Med (2021). https://doi.org/10.1007/s12017-021-08648-0

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Keywords

  • Microarray
  • Drug-resistant epilepsy
  • Convulsion
  • Neurological
  • Cholesterol