Expression Profiles of TRIM Family Genes in Neuronal and Glial Cell Cultures of Healthy Donors and Patients with Parkinson’s Disease under Normal Conditions and Upon Neuroinflammation

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Abstract

Proteins of the TRIM family are involved in both innate immunity and the nervous system processes and may play an important role in the development of neurodegenerative diseases. In this work, we analyzed the expression of 35 genes of the TRIM family in neural progenitors (NPs), terminally differentiated neurons (TDNs) and glial derivatives (NGs) obtained from induced pluripotent stem cells (iPSCs) of healthy donors (HD) and patients with Parkinson’s disease (PD), in the absence of inflammatory stimuli and upon the induction of a nonspecific inflammatory response under the influence of TNFα. In NPs and TDNs of PD patients, compared with HD cells, differences in expression were observed for only a small number of TRIM genes. Under the influence of TNFα in TDNs, the expression of individual TRIM genes was activated, which was more significant in the cells of patients with PD compared to cells of HDs. In NGs of PD patients, the expression of many TRIM genes was initially reduced compared to HD cells and remained low or further decreased after exposure to TNFα. The data obtained demonstrate differences in the network of the TRIM family members in PD neurons and glia compared to control, and also show the multidirectional influence of the inflammatory stimulus on the expression of a number of TRIM genes in these types of cells. Considering the important role of many TRIM genes in the functioning of the innate immune system, it can be assumed that, in PD, more significant disturbances in the functioning of genes of this family occur in glia compared to neurons.

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About the authors

V. V. Nenasheva

Kurchatov Institute

Email: katishsha@mail.ru
Russian Federation, Moscow, 123182

Е. V. Novosadova

Kurchatov Institute

Email: katishsha@mail.ru
Russian Federation, Moscow, 123182

T. P. Gerasimova

Lopukhin Federal Research and Clinical Center of Physical Chemical Medicine of the Federal Medical and Biological Agency of the Russian Federation

Email: katishsha@mail.ru
Russian Federation, Moscow, 119435

L. V. Novosadova

Kurchatov Institute

Email: katishsha@mail.ru
Russian Federation, Moscow, 123182

A. Yu. Kotok

Kurchatov Institute

Email: katishsha@mail.ru
Russian Federation, Moscow, 123182

E. L. Arsenyeva

Kurchatov Institute

Email: katishsha@mail.ru
Russian Federation, Moscow, 123182

Е. А. Stepanenko

Kurchatov Institute

Author for correspondence.
Email: katishsha@mail.ru
Russian Federation, Moscow, 123182

I. А. Grivennikov

Kurchatov Institute

Email: katishsha@mail.ru
Russian Federation, Moscow, 123182

V. Z. Tarantul

Kurchatov Institute

Email: katishsha@mail.ru
Russian Federation, Moscow, 123182

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3. Fig. 1. PCR analysis of TRIM family gene expression in NP (a), TDH (b) and NG (c) healthy donors (PD) and patients with PD (PD). *p < 0.05, **p < 0.01, ***p < 0.001. The 18S rRNA gene was used as a reference.

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4. Fig. 2. Analysis of TRIM9 gene protein (a) and mRNA (b) levels in NP, TDN, and NG of healthy donors and patients with Parkinson's disease (PD). The reference protein is GAPDH.

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5. Fig. 3. PCR analysis of TRIM gene expression in NG obtained from PD patients and healthy donors, normally and 24 hours after TNFα inflammation stimulation (10 ng/ml).The 18S rRNA gene was used as a reference gene. *p < 0.05, **p < 0.01, ***p < 0.001.

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6. Fig. 4. PCR analysis of TRIM gene expression in PD patients and healthy donors, normal and 24 hours after TNFα inflammation stimulation (20 ng/ml). The reference gene is 18S rRNA. *p < 0.05, **p < 0.01, ***p < 0.001.

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