Early Induction of Neurotrophin Receptor and miRNA Genes in Mouse Brain after Pentilenetetrazole-Induced Neuronal Activity

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Anna A. Shmakova^1,2, Karina D. Rysenkova^1,2, Olga I. Ivashkina^3,4,5, Anna M. Gruzdeva³, Polina S. Klimovich^1,2, Vladimir S. Popov¹, Kseniya A. Rubina¹, Konstantin V. Anokhin^3,4,a, Vsevolod A. Tkachuk^1,2, and Ekaterina V. Semina^1,2,b*

¹Faculty of Medicine, Lomonosov Moscow State University, 119192 Moscow, Russia

²Institute of Experimental Cardiology, National Cardiology Research Center of the Ministry of Health of the Russian Federation, 121552 Moscow, Russia

³Institute for Advanced Brain Studies, Lomonosov Moscow State University, 119192 Moscow, Russian Federation

⁴Anokhin Research Institute of Normal Physiology, 125315 Moscow, Russia

⁵Kurchatov Institute National Research Center, 123182 Moscow, Russia

^* To whom correspondence should be addressed.

Received November 23, 2020; Revised June 21, 2021; Accepted June 30, 2021

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Neurotrophin receptors regulate neuronal survival and network formation, as well as synaptic plasticity in the brain via interaction with their ligands. Here, we examined early changes in the expression of neurotrophin receptor genes Ntk1 (TrkA), Ntrk2 (TrkB), Ntrk3 (TrkC), Ngfr (p75NTR) and miRNAs that target theses gens in the mouse brain after induction of seizure activity by pentylenetetrazol. We found that expression of Ntrk3 and Ngfr was upregulated in the cortex and the hippocampus 1-3 hours after the seizures, while Ntrk2 expression increased after 3-6 hours in the anterior cortex and after 1 and 6 hours in the hippocampus. At the same time, the ratio of Bcl-2/Bax signaling proteins increased in the anterior and posterior cortex, but not in the hippocampus, suggesting the activation of anti-apoptotic signaling. Expression of miRNA-9 and miRNA-29a, which were predicted to target Ntrk3, was upregulated in the hippocampus 3 hours after pentylenetetrazol injection. Therefore, early cellular response to seizures in the brain includes induction of the Ntrk2, Ntrk3, Ngfr, miRNA-9, and miRNA-29a expression, as well as activation of Bcl-2 and Bax signaling pathways, which may characterize them as important mediators of neuronal adaptation and survival upon induction of the generalized brain activity.

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KEY WORDS: neurotrophin receptors, TrkA, TrkB, TrkC, p75NTR, miRNAs, miRNA-9, miRNA-29a, early response genes, neuronal activation, apoptosis

DOI: 10.1134/S0006297921100138

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