Alterations in the transcriptional profile of genes related 
to glutamatergic signalling in animal models of Alzheimer’s disease. The effect of fingolimod

Grzegorz Sulkowski; Przemysław Leonard Wencel; Beata Dąbrowska-Bouta; Lidia Struzynska; Robert Strosznajder

doi:10.5114/fn.2022.114302

eISSN: 1509-572x
ISSN: 1641-4640

Folia Neuropathologica

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abstract:

Original paper

Alterations in the transcriptional profile of genes related to glutamatergic signalling in animal models of Alzheimer’s disease. The effect of fingolimod

Grzegorz Sulkowski

¹

,

Przemysław Leonard Wencel

²

,

Beata Dąbrowska-Bouta

¹

,

Lidia Struzynska

¹

,

Robert Strosznajder

²

Laboratory of Pathoneurochemistry, Department of Neurochemistry, Mossakowski Medical Research Institute, Polish Academy of Sciences, Warsaw, Poland
Laboratory of Preclinical Research and Environmental Agents, Mossakowski Medical Research Institute, Polish Academy of Sciences, Warsaw, Poland

Folia Neuropathol 2022; 60 (1): 10-23

DOI: https://doi.org/10.5114/fn.2022.114302

Online publish date: 2022/03/29

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AMA

Sulkowski G, Wencel P, Dąbrowska-Bouta B, Struzynska L, Strosznajder R. Alterations in the transcriptional profile of genes related 
to glutamatergic signalling in animal models of Alzheimer’s disease. The effect of fingolimod. Folia Neuropathologica. 2022;60(1):10-23. doi:10.5114/fn.2022.114302.

APA

Sulkowski, G., Wencel, P., Dąbrowska-Bouta, B., Struzynska, L.,  & Strosznajder, R. (2022). Alterations in the transcriptional profile of genes related 
to glutamatergic signalling in animal models of Alzheimer’s disease. The effect of fingolimod. Folia Neuropathologica, 60(1), 10-23. https://doi.org/10.5114/fn.2022.114302

Chicago

Sulkowski, Grzegorz, Przemysław Leonard Wencel, Beata Dąbrowska-Bouta, Lidia Struzynska,  and Robert Strosznajder. 2022. "Alterations in the transcriptional profile of genes related 
to glutamatergic signalling in animal models of Alzheimer’s disease. The effect of fingolimod". Folia Neuropathologica 60 (1): 10-23. doi:10.5114/fn.2022.114302.

Harvard

Sulkowski, G., Wencel, P., Dąbrowska-Bouta, B., Struzynska, L.,  and Strosznajder, R. (2022). Alterations in the transcriptional profile of genes related 
to glutamatergic signalling in animal models of Alzheimer’s disease. The effect of fingolimod. Folia Neuropathologica, 60(1), pp.10-23. https://doi.org/10.5114/fn.2022.114302

MLA

Sulkowski, Grzegorz et al. "Alterations in the transcriptional profile of genes related 
to glutamatergic signalling in animal models of Alzheimer’s disease. The effect of fingolimod." Folia Neuropathologica, vol. 60, no. 1, 2022, pp. 10-23. doi:10.5114/fn.2022.114302.

Vancouver

Sulkowski G, Wencel P, Dąbrowska-Bouta B, Struzynska L, Strosznajder R. Alterations in the transcriptional profile of genes related 
to glutamatergic signalling in animal models of Alzheimer’s disease. The effect of fingolimod. Folia Neuropathologica. 2022;60(1):10-23. doi:10.5114/fn.2022.114302.

PlumX metrics:

Alzheimer’s disease (AD) is a multi-factorial illness that leads to progressive cognitive impairment. A glutamatergic system dysfunction has been reported to be implicated in the pathomechanism of AD. Therefore, in the current study we characterized the transcriptional profile of glutamate-related genes in transgenic AbPP V717I (TgAD) and sporadic (SAD, streptozotocin-induced) models of AD. Genes encoding glutamate membrane-bound (GLAST, GLT1, EAAC1) and vesicular (VGLUT1-3) transporters as well as ionotropic (AMPA, NMDA) and metabotropic (mGluR3, mGluR5) receptors were analysed. Based on qPCR analysis, we observed a discrepancy between TgAD and SAD mice in the profile of targeted genes. We noticed age-dependent upregulation of genes encoding VGLUT1, NMDAR1 and mGluR3 in 12-month-old TgAD mice. In the SAD model upregulation of genes encoding AMPAR1 and NMDAR1 as well as downregulation of GLAST, VGLUT3 and mGluR5 were found. Next, the effect of fingolimod (FTY720) was indicated. In the TgAD model, the drug reversed altered transcription of the mGluR3 glutamate receptor to the control level, whereas in the SAD model it downregulated the genes encoding VGLUT1, AMPAR2 and mGluR3. Interestingly, FTY720 influenced mGluR3 mRNA in both examined models. Observed alterations of gene transcription and the effects of FTY720 may potentially constitute an interesting target for further pharmacological studies.

keywords:

Alterations in the transcriptional profile of genes related to glutamatergic signalling in animal models of Alzheimer’s disease. The effect of fingolimod

Grzegorz Sulkowski 1 , Przemysław Leonard Wencel 2 , Beata Dąbrowska-Bouta 1 , Lidia Struzynska 1 , Robert Strosznajder 2

Alzheimer’s disease, sphingosine-1-phosphate, streptozotocin, glutamate transporters, glutamate receptors, FTY720

Grzegorz Sulkowski

¹

,

Przemysław Leonard Wencel

²

,

Beata Dąbrowska-Bouta

¹

,

Lidia Struzynska

¹

,

Robert Strosznajder

²