ИСТИНА

Retrotransposons, the DNA elements which proliferate by reverse transcription of their RNA intermediates, comprise a major fraction of mammalian genomes. In the human genome a particularly abundant retrotransposon - long interspersed nuclear element-1 (LINE-1 or L1) has 5x105 copies 80–100 of which are active and competent for retrotransposition. Recent findings indicate that LINE-1 is active in neuronal precursor cells during differentiation, and its de novo insertions can change expression of neuron-specific genes and cause somatic mosaicism in the adult brain. However, there has been limited understanding whether such retrotranspositions happen in the adult brain, when and how they occur, and what is their importance for the CNS function. In our study we tested whether prolonged stress, wheel running, or operant learning can lead to changes in L1 DNA copy number in the mouse brain. For this purpose, we subjected mice to immobilization stress (2 hours a day, 10 days), wheel running (unlimited access, 10 days) or nose-poke operant training (1 session a day, 10 days). We collected the samples of hippocampus, frontal cortex, cerebellum, muscle and testicle tissues from experimental and home cage control mice. We performed qPCR for analysis of 3’-UTR and ORF-1 copy number. We observed significant increase in the 3’-UTR and ORF-1 copy number in all brain structures of the stress group compared to the home cage group. Nose-poke training was associated with specific increase in 3’-UTR copy number in the hippocampus. We also observed a small increase in 3’-UTR and ORF-1 copy number in all investigated brain structures in wheel running group. Altogether our results show that retrotranspositions is a common event in the adult brain under different conditions of novel experience.