The effect of a sphingosine-1-phosphate receptors modulator on the transcriptional profile of genes linked to glutamate homeostasis in the sporadic and genetic animal models of Alzheimer’s disease

• Autorzy: Wencel P. , Sulkowski G. , Dabrowska-Bouta B. , Strosznajder R.P. , Struzynska L.
• Języki publikacji: EN

Abstrakty

EN

INTRODUCTION: Alzheimer’s disease (AD) is neurodegenerative disorder characterized by progressive memory impairment and cognitive failure which leads to dementia in aged population. Lots of data indicate glutamate-mediated neurotoxicity as a one of the pathomechanisms responsible for neuronal cell death during the course of AD. AIM(S): In this study, we examined the effect of fingolimod (FTY720‑modulator of sphingosine‑1‑phosphate receptors) on the transcription of genes involved in the homeostasis of glutamatergic system in animal models of AD. METHOD(S): 3‑ and 12‑month‑old (3M, 12M) FVB/ APP+ transgenic mice with the London (V717I) APP mutation were used in this study. Mice without the mutation (APP- ) were used as a control. The sporadic AD model was induced by injection of streptozotocin (STZ, icv. 2,5 mg/kg b.w.) in ACSF (vehicle) to 3M C57BL/6 mice. Animals received FTY720 (1mg/kg b.w.) or NaCl (vehicle) for 2 weeks. Brain cortex was isolated and qPCR methods were applied. RESULTS: Our results indicate a different model‑dependent profile of changes in gene expression. We observed significant upregulation of Slc17a7(VGluT1), Grin1(- GluN1), and Grm3 (mGluR3) gene expression in APP+ 12M mice. A significant elevation of Gria1(GluR‑1) and Grin1 (GluN1) mRNA levels with an accompanying decrease of Slc17a8 (VGluT3) and Grm5 (mGluR5) was observed in STZ mice. The administration of FTY720 led to a decrease in Gria2 (GluR-2) and Grm3 mRNA levels, as well as, an elevation of Slc1a3 (GluT‑1), Slc17a7, and Slc17a8 mRNA in STZ mice compared to appropriate controls. Transcriptional changes in vesicular glutamate transporters (Slc17a7 and Slc17a8) as well as glutamate receptors genes (Grin1, Gria1, Grm3,5) suggest that they may be involved in the mechanisms leading to AD. CONCLUSIONS: FTY720 may potentially modulate the expression of genes involved in homeostasis of the glutamatergic system in the model of sporadic AD. FINANCIAL SUPPORT: Supported by the National Science Centre grant no. NCN2014/15/B/NZ3/01049

• Wydawca: -
• Czasopismo: Acta Neurobiologiae Experimentalis
• Rocznik: 2019
• Tom: 79
• Numer: Suppl.1
• Opis fizyczny: p.LXXX

Twórcy

autor

Wencel P.

• Laboratory of Preclinical Research and Environmental Agents, Department of Neurosurgery, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland

autor

Sulkowski G.

• Laboratory of Pathoneurochemistry, Department of Neurochemistry, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland

autor

Dabrowska-Bouta B.

• Laboratory of Pathoneurochemistry, Department of Neurochemistry, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland

autor

Strosznajder R.P.

• Laboratory of Preclinical Research and Environmental Agents, Department of Neurosurgery, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland

autor

Struzynska L.

• Laboratory of Pathoneurochemistry, Department of Neurochemistry, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland