Telomerase might have an important role in the mechanism of action of various psychiatric medications


Telomeres is the region at the end of each strand of DNA that protects our chromosomes from deterioration, its role is to provide chromosomal stability and genomic integrity. Telomere shortening has been associated with senescence, cell death and disease on the other hand, telomerase length (TL) might help with the understanding of general health, life expectancy and individual aging.

Some recent preclinical studies suggest a link between telomerase activity and psychiatric medication. Telomerase is a reverse transcriptase enzyme that add repeats sequence “TTAGGG” in the telomeres region of the chromosome. Telomerase is formed of two main elements:

1) Telomerase RNA element (TERC), which serves as a RNA template for telomeric DNA synthesis

2) Telomerase reverse transcriptase (TERT), whose function is adding telomeric repeats.

Thalia Figure 1 2-12-15

In a recent paper Bersani and co-workers review the recent clinical and preclinical data in which they suggest a link in telomerase activity in psychopharmacological interventions. For example, in a preclinical rodent study (Zhou, et al. 2011) they found that hippocampal (HC) telomerase might be implicated in the regulation of depression like behaviour. Mice with chronic mild stress (CMS) presented a reduced HC telomerase activity compared to the control group, while inhibition of telomerase activity resulted in depression like phenotype, but most importantly they also found that overexpression of TERT resulted in antidepressive like effects. However, the telomerase activity is regulated in different manner in humans. A pilot study with humans (Wolkowitz et al., 2012) showed a possible link between telomerase activity and antidepressant medication, patients with major depressive disorder (MDD) increased peripheral blood mononuclear cells (PBMC) telomerase activity when treatment is administered (Sertraline therapy), they suggest a link between the increased levels of telomerase activity and antidepressant treatment. Another study in humans (Martisson et al. 2013) showed that long term lithium treatment (30 months) in patients with bipolar disorder presented longer leukocyte telomere length compared to patients with shorter period of treatment, suggesting that lithium treatment might preserve against telomere shortening by induction of telomerase activity. There are different hypotheses on why telomerase activity might be linked to psychiatric medications, the diagram below shows some of the proposed mechanism of actions between these interactions, which includes some regulation pathways involved in cell proliferation, differentiation and oxidative stress.

Thalia Figure 2 2-12-15

The study of telomere biology and telomerase activity in the body is complex, more data and further research is necessary in order to understand the interaction with psychopharmacological interventions, however it might be a new promising area of study to develop novel drugs targeting telomerase activity in mental disorders.

Blog written by Thalia Carreno

References

Bersani, F.S. et al. (2015) Telomerase activation as a possible mechanism of action for psychopharmacological interventions. Drug Discov Today. 20, 1305-1309

Martinsson, L. et al. (2013) Long-term lithium treatment in bipolar disorder is associated with longer leukocyte telomeres. Transl. Psychiatry 3, e261

Wolkowitz, O.M. et al. (2012) Resting leukocyte telomerase activity is elevated in major depression and predicts treatment response. Mol. Psychiatry 17, 164–172

Zhou, Q.G. et al. (2011) Hippocampal telomerase is involved in the modulation of depressive behaviors. J. Neurosci. 31, 12258–12269

 

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