Effects of early life stress on neurogenic brain regions: activity of LINE-1 retrotransposons decreases in hippocampal neurons in rats subjected to neonatal-maternal separation

MARIANA SALCEDO; ANDRES J ORQUEDA

Congreso; Reunión conjunta SAIC-SAI 2016; 2016

Long Interspersed Nuclear Elements-1 (LINE-1) retrotransposons are repetitive elements that encode an RNA binding protein (ORF1p) and an endonuclease with reverse transcriptase activity (ORF2p), that control LINE-1 mobilization via target prime reverse transcription. Despite most human LINE-1 insertions occur during early embryonic development, somatic retrotransposition also takes place in the brain. Thus, by inserting into new genomic locations, LINE-1 activity is a potential source of genotypic variation among neurons. In humans, the consequences of somatic mosaicism are most apparent in disease, including many neuropsychiatric disorders (e.g. Rett syndrome and schyzophrenia) and cancer, which show increased LINE-1 activity. Thus, the possibility that LINE-1-driven somatic mosaicism alters functional properties of the brain arises. On the other hand, the formation of neuronal networks is also affected by adverse early life experiences. Indeed, it is known that in vivo neonatal maternal separation (NMS) attenuates the capacity of adult hippocampal neuronal precursor cells to differentiate into neurons. However, the precise mechanism of this process is still poorly understood. In this study we examined how NMS impacts on the activity of LINE-1 in adult hippocampal neuronal precursor cells. We found that relative ORF2 DNA content is significantly reduced in hippocampal tissue of adult rats subjected to NMS, suggesting a reduction of new LINE-1 insertions. Relative ORF2 DNA content was not affected in the cerebellum, a non-neurogenic brain region. In addition, behavioral tests were used to evaluate cognitive functions: preliminary results of episodic-like memory and anxiety tests show no significant difference. Taken together, these findings show that retrotransposition of LINE-1 in rats is negatively affected by early life stress of pups, and suggest that altered hippocampal neurogenesis by NMS is associated to a decreased LINE-1 activity.