Top

Published in:

01-12-2021 | Epilepsy | Original Paper

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

Authors: Sridhar Amalakanti, Unis Ahmad Bhat, Madhavi B. Mylavarapu, Nitin Khandelwal, N. V. Sundarachary, Sumana Chakravarty, Arvind Kumar

Published in: NeuroMolecular Medicine | Issue 4/2021

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.

Available only for authorised users

Alves, M., Gomez-Villafuertes, R., Delanty, N., Farrell, M. A., O’Brien, D. F., Miras-Portugal, M. T., et al. (2017). Expression and function of the metabotropic purinergic P2Y receptor family in experimental seizure models and patients with drug-refractory epilepsy. Epilepsia, 58(9), 1603–1614. https://doi.org/10.1111/epi.13850.CrossRefPubMed

Brandt, C., Bethmann, K., Gastens, A. M., & Loscher, W. (2006). The multidrug transporter hypothesis of drug resistance in epilepsy: Proof-of-principle in a rat model of temporal lobe epilepsy. Neurobiology of Diseases, 24(1), 202–211. https://doi.org/10.1016/j.nbd.2006.06.014.CrossRef

Chali, F., Djelti, F., Eugene, E., Valderrama, M., Marquer, C., Aubourg, P., et al. (2015). Inhibiting cholesterol degradation induces neuronal sclerosis and epileptic activity in mouse hippocampus. European Journal of Neuroscience, 41(10), 1345–1355. https://doi.org/10.1111/ejn.12911.CrossRef

Cheng, D., Jenner, A. M., Shui, G., Cheong, W. F., Mitchell, T. W., Nealon, J. R., et al. (2011). Lipid pathway alterations in Parkinson’s disease primary visual cortex. PLoS ONE, 6(2), e17299. https://doi.org/10.1371/journal.pone.0017299.CrossRefPubMedPubMedCentral

del Toro, D., Xifro, X., Pol, A., Humbert, S., Saudou, F., Canals, J. M., et al. (2010). Altered cholesterol homeostasis contributes to enhanced excitotoxicity in Huntington’s disease. Journal of Neurochemistry, 115(1), 153–167. https://doi.org/10.1111/j.1471-4159.2010.06912.x.CrossRefPubMed

Etminan, M., Samii, A., & Brophy, J. M. (2010). Statin use and risk of epilepsy: A nested case-control study. Neurology, 75(17), 1496–1500. https://doi.org/10.1212/WNL.0b013e3181f96253.CrossRefPubMed

Karasinska, J. M., & Hayden, M. R. (2011). Cholesterol metabolism in Huntington disease. Nature Reviews Neurology, 7(10), 561–572. https://doi.org/10.1038/nrneurol.2011.132.CrossRefPubMed

Khandelwal, N., Dey, S. K., Chakravarty, S., & Kumar, A. (2019). miR-30 family miRNAs mediate the effect of chronic social defeat stress on hippocampal neurogenesis in mouse depression model. Frontiers in Molecular Neuroscience, 12, 188. https://doi.org/10.3389/fnmol.2019.00188.CrossRefPubMedPubMedCentral

Kwan, P., Schachter, S. C., & Brodie, M. J. (2011). Drug-resistant epilepsy. New England Journal of Medicine, 365(10), 919–926. https://doi.org/10.1056/NEJMra1004418.CrossRef

Mercado-Gomez, O. F., Cordova-Davalos, L., Garcia-Betanzo, D., Rocha, L., Alonso-Vanegas, M. A., Cienfuegos, J., et al. (2018). Overexpression of inflammatory-related and nitric oxide synthase genes in olfactory bulbs from frontal lobe epilepsy patients. Epilepsy Research, 148, 37–43. https://doi.org/10.1016/j.eplepsyres.2018.09.012.CrossRefPubMed

Quintana-Pajaro, L. J., Ramos-Villegas, Y., Cortecero-Sabalza, E., Joaquim, A. F., Agrawal, A., Narvaez-Rojas, A. R., et al. (2018). The effect of statins in epilepsy: A systematic review. Journal of Neuroscience and Rural Practice, 9(4), 478–486. https://doi.org/10.4103/jnrp.jnrp_110_18.CrossRef

Shao, Y., Wang, C., Hong, Z., & Chen, Y. (2016). Inhibition of p38 mitogen-activated protein kinase signaling reduces multidrug transporter activity and anti-epileptic drug resistance in refractory epileptic rats. Journal of Neurochemistry, 136(5), 1096–1105. https://doi.org/10.1111/jnc.13498.CrossRefPubMed

Srivastava, N. K., Mukherjee, S., Sharma, R., Das, J., Sharma, R., Kumar, V., et al. (2019). Altered lipid metabolism in post-traumatic epileptic rat model: One proposed pathway. Molecular Biology Reports, 46(2), 1757–1773. https://doi.org/10.1007/s11033-019-04626-9.CrossRefPubMed

Tang, F., Hartz, A. M. S., & Bauer, B. (2017). Drug-resistant epilepsy: Multiple hypotheses, few answers. Frontiers in Neurology, 8, 301. https://doi.org/10.3389/fneur.2017.00301.CrossRefPubMedPubMedCentral

Wang, Y., Du, X., Bin, R., Yu, S., Xia, Z., Zheng, G., et al. (2017). Genetic variants identified from epilepsy of unknown etiology in Chinese children by targeted exome sequencing. Scientific Reports, 7, 40319. https://doi.org/10.1038/srep40319.CrossRefPubMedPubMedCentral

Title: Gene Expression Analysis Identifies Cholesterol Metabolism Dysregulation in Hippocampus of Phenytoin-Resistant Pentylenetetrazol-Kindled Epileptic Mice
Authors: Sridhar Amalakanti
Unis Ahmad Bhat
Madhavi B. Mylavarapu
Nitin Khandelwal
N. V. Sundarachary
Sumana Chakravarty
Arvind Kumar
Publication date: 01-12-2021
Publisher: Springer US
Keywords: Epilepsy
Phenytoin
Published in: NeuroMolecular Medicine / Issue 4/2021
Print ISSN: 1535-1084
Electronic ISSN: 1559-1174
DOI: https://doi.org/10.1007/s12017-021-08648-0

Keynote webinar | Spotlight on medication adherence

Springer Medicine

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

Abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 4/2021

IL-2/IL-2R Antibody Complex Enhances Treg-Induced Neuroprotection by Dampening TNF-α Inflammation in an In Vitro Stroke Model

Ubiquitination of p21 by E3 Ligase TRIM21 Promotes the Proliferation of Human Neuroblastoma Cells

Overexpression of microRNA-939-5p Contributes to Cell Proliferation and Associates Poor Prognosis in Glioma

Vitamin D3 Supplement Attenuates Blood–Brain Barrier Disruption and Cognitive Impairments in a Rat Model of Traumatic Brain Injury

Retraction Note to: Methylation and Expression Patterns of Tropomyosin-Related Kinase Genes in Different Grades of Glioma

Correction to: Specific Susceptibility to COVID-19 in Adults with Down Syndrome