| 1. |
- Bersani, Francesco S, et al.
(författare)
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Telomerase activation as a possible mechanism of action for psychopharmacological interventions.
- 2015
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Ingår i: Drug Discovery Today. - : Elsevier BV. - 1878-5832 .- 1359-6446. ; 20:11, s. 1305-1309
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Forskningsöversikt (refereegranskat)abstract
- Originally studied in relation to aging and cancer research, telomerase is now also investigated in relation to psychiatric disorders and treatments. Based on emerging clinical and preclinical data, we hypothesise that telomerase activation could represent a novel element mediating the mechanism of action of certain psychopharmacological interventions (e.g. antidepressants, lithium and antipsychotics). The modulation of intracellular Wnt/β-catenin or PI3K/Akt signalling pathways, the interaction with BDNF and 5-HT, and the antioxidant properties could represent possible mechanisms by which the different types of psychiatric medications could modulate telomerase activity. The potential of telomerase in promoting cellular survival and/or function in the brain and in the periphery could, in turn, represent a neurobiological substrate through which the enzyme can mediate the therapeutic effect of such interventions.
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| 2. |
- Lindqvist, Daniel, et al.
(författare)
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Psychiatric disorders and leukocyte telomere length: Underlying mechanisms linking mental illness with cellular aging.
- 2015
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Ingår i: Neuroscience and Biobehavioral Reviews. - : Elsevier BV. - 0149-7634. ; 55:May 18, s. 333-364
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Forskningsöversikt (refereegranskat)abstract
- Many psychiatric illnesses are associated with early mortality and with an increased risk of developing physical diseases that are more typically seen in the elderly. Moreover, certain psychiatric illnesses may be associated with accelerated cellular aging, evidenced by shortened leukocyte telomere length (LTL), which could underlie this association. Shortened LTL reflects a cell's mitotic history and cumulative exposure to inflammation and oxidation as well as the availability of telomerase, a telomere-lengthening enzyme. Critically short telomeres can cause cells to undergo senescence, apoptosis or genomic instability, and shorter LTL correlates with poorer health and predicts mortality. Emerging data suggest that LTL may be reduced in certain psychiatric illnesses, perhaps in proportion to exposure to the psychiatric illnesses, although conflicting data exist. Telomerase has been less well characterized in psychiatric illnesses, but a role in depression and in antidepressant and neurotrophic effects has been suggested by preclinical and clinical studies. In this article, studies on LTL and telomerase activity in psychiatric illnesses are critically reviewed, potential mediators are discussed, and future directions are suggested. A deeper understanding of cellular aging in psychiatric illnesses could lead to re-conceptualizing them as systemic illnesses with manifestations inside and outside the brain and could identify new treatment targets.
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| 3. |
- Wolkowitz, Owen M, et al.
(författare)
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PBMC telomerase activity, but not leukocyte telomere length, correlates with hippocampal volume in major depression.
- 2015
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Ingår i: Psychiatry Research. - : Elsevier BV. - 1872-7123 .- 0925-4927. ; 232:1, s. 58-64
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Tidskriftsartikel (refereegranskat)abstract
- Accelerated cell aging, indexed in peripheral leukocytes by telomere shortness and in peripheral blood mononuclear cells (PBMCs) by telomerase activity, has been reported in several studies of major depressive disorder (MDD). However, the relevance of these peripheral measures for brain indices that are presumably more directly related to MDD pathophysiology is unknown. In this study, we explored the relationship between PBMC telomerase activity and leukocyte telomere length and magnetic resonance imaging-estimated hippocampal volume in un-medicated depressed individuals and healthy controls. We predicted that, to the extent peripheral and central telomerase activity are directly related, PBMC telomerase activity would be positively correlated with hippocampal volume, perhaps due to hippocampal telomerase-associated neurogenesis, neuroprotection or neurotrophic facilitation, and that this effect would be clearer in individuals with increased PBMC telomerase activity, as previously reported in un-medicated MDD. We did not have specific hypotheses regarding the relationship between leukocyte telomere length and hippocampal volume, due to conflicting reports in the published literature. We found, in 25 un-medicated MDD subjects, that PBMC telomerase activity was significantly positively correlated with hippocampal volume; this relationship was not observed in 18 healthy controls. Leukocyte telomere length was not significantly related to hippocampal volume in either group (19 unmedicated MDD subjects and 17 healthy controls). Although the nature of the relationship between peripheral telomerase activity and telomere length and the hippocampus is unclear, these preliminary data are consistent with the possibility that PBMC telomerase activity indexes, and may provide a novel window into, hippocampal neuroprotection and/or neurogenesis in MDD.
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