Telomerase dysregulation in the hippocampus of a rat model of depression. Normalization by lithium

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  • Yabin Wei
  • ,
  • Lena Backlund
  • ,
  • Gregers Wegener
  • Aleksander A Mathe
  • ,
  • Catharina Lavebratt

Background: Telomeres are protective DNA-protein complexes at the ends of each chromosome, maintained primarily by the enzyme telomerase. Shortening of the blood leukocyte telomeres (LT) is associated with aging, several chronic diseases and stress, e.g. major depression. Hippocampus is pivotal in the regulation of cognition and mood and the main brain region of telomerase activity. Whether there is telomere dysfunction in the hippocampus of depressed subjects is unknown. Lithium, used in the treatment and relapse prevention of mood disorders, was found to protect against LT shortening in humans, but the mechanism has not been elucidated. To answer the questions whether telomeres are shortened and the telomerase activity changed in the hippocampus and whether lithium could reverse the process, we used a genetic model of depression, the Flinders Sensitive Line (FSL) rat and treated the animals with lithium. Methods: Telomere length (TL), telomerase reverse transcriptase (Tert) expression, telomerase activity and putative mediators of telomerase activity were investigated in the hippocampus of these animals. Results: The naïve FSL had shorter TL, downregulated Tert expression, reduced BDNF levels and telomerase activity compared with the Flinders Resistant Line (FRL) controls. Lithium treatment normalized the Tert expression and telomerase activity in the FSL, and upregulated β-catenin. Conclusion: This is the first report showing telomere dysregulation in hippocampus of a well-defined depression model and restorative effects of lithium treatment. If replicated in other models of mood disorder, the findings will contribute to understanding both the telomere function and the mechanism of lithium action in hippocampus of depressed patients.

Original languageEnglish
JournalInternational Journal of Neuropsychopharmacology
Number of pages1
ISSN1461-1457
DOIs
Publication statusPublished - 2015

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