Telomerase levels in schizophrenia: A preliminary study

Porton, Barbara; DeLisi, Lynn E.; Bertisch, Hilary; Ji, Fei; Gordon, Derek; Li, Ping; Benedict, Melissa M.; Greenberg, William M.; Kao, Hung‐Teh

doi:10.1016/j.schres.2008.08.028

Cited by 52 publications

(34 citation statements)

References 37 publications

(48 reference statements)

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“…CAG treatment also elicited significant telomerase and CREB activation in PC12 cells and primary neuronal cultures, which could account for its antidepressant effect. Accumulating evidence suggests that psychological and metabolic stress can lead to telomere dysfunction [15,16,17,18]. Stressed individuals usually exhibit reduced telomerase activity and accelerated telomere shortening compared to low-stress controls [15,18].…”

Section: Discussionmentioning

confidence: 99%

“…Stressed individuals usually exhibit reduced telomerase activity and accelerated telomere shortening compared to low-stress controls [15,18]. In particular, significant telomere erosion is reported in patients with psychiatric disorders such as schizophrenia, mood disorders, and pathological cognitive aging including Alzheimer's disease and dementias [15,16,17,18]. Taken together, these findings suggest that telomerase reconstitution (e.g., by CAG) is a potential strategy for retarding disease progression.…”

Section: Discussionmentioning

confidence: 99%

“…Aged telomerase RNA-knockout mice with telomere dysfunction exhibit memory deficits [13,14]. The telomere length of peripheral blood lymphocytes has recently been proposed to be a biomarker of individuals suffering from chronic stress, depression, schizophrenia, and pathological cognitive decline as observed in Alzheimer's disease and dementias [15,16,17,18]. These findings demonstrate that psychological disorders and neurodegenerative diseases are related to telomere shortening.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Cycloastragenol Is a Potent Telomerase Activator in Neuronal Cells: Implications for Depression Management

Ip¹,

Ng²,

An³

et al. 2014

Neurosignals

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Cycloastragenol (CAG) is an aglycone of astragaloside IV. It was first identified when screening Astragalus membranaceus extracts for active ingredients with antiaging properties. The present study demonstrates that CAG stimulates telomerase activity and cell proliferation in human neonatal keratinocytes. In particular, CAG promotes scratch wound closure of human neonatal keratinocyte monolayers in vitro. The distinct telomerase-activating property of CAG prompted evaluation of its potential application in the treatment of neurological disorders. Accordingly, CAG induced telomerase activity and cAMP response element binding (CREB) activation in PC12 cells and primary neurons. Blockade of CREB expression in neuronal cells by RNA interference reduced basal telomerase activity, and CAG was no longer efficacious in increasing telomerase activity. CAG treatment not only induced the expression of bcl2, a CREB-regulated gene, but also the expression of telomerase reverse transcriptase in primary cortical neurons. Interestingly, oral administration of CAG for 7 days attenuated depression-like behavior in experimental mice. In conclusion, CAG stimulates telomerase activity in human neonatal keratinocytes and rat neuronal cells, and induces CREB activation followed by tert and bcl2 expression. Furthermore, CAG may have a novel therapeutic role in depression. © 2014 S. Karger AG, Basel

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Cycloastragenol Is a Potent Telomerase Activator in Neuronal Cells: Implications for Depression Management

Ip¹,

Ng²,

An³

et al. 2014

Neurosignals

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“…Consistent with previous meta-analyses, 17,19 findings were mixed. Five reports found that TL and telomerase activity were decreased in schizophrenia, 29,34,36,42,49 3 observed no difference in TL between schizophrenia and HC groups, 31,32,51 and one reported increased TL in schizophrenia. 33 Wolkowitz et al 47 found a group × gender interaction, such that HC women had longer TL than women with schizophrenia.…”

Section: Characteristics Of Reviewed Studiesmentioning

confidence: 95%

Systemic Biomarkers of Accelerated Aging in Schizophrenia: A Critical Review and Future Directions

Nguyen

Eyler

Jeste

2017

Schizophrenia Bulletin

104

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Background: Schizophrenia is associated with increased physical morbidity and early mortality, suggesting that the aging process may be accelerated in schizophrenia. However, the biological underpinnings of these alterations in aging in schizophrenia are unclear. Method: We conducted a detailed search of peer-reviewed empirical studies to evaluate evidence for accelerated biological aging in schizophrenia based on systemic, age-related biomarkers. We included studies that investigated differences between persons with schizophrenia and healthy comparison subjects in levels of biomarkers known to be associated with aging and examined the relationship of these biomarkers to age in the 2 groups. Results: Forty-two articles that met our selection criteria were reviewed. Nearly 75% reported abnormal biomarker levels among individuals with schizophrenia, including indices of inflammation, cytotoxicity, oxidative stress, metabolic health, gene expression, and receptor/synaptic function, with medium to large effect sizes reported in many studies. Twenty-nine percent of the studies observed differential age-related decline in schizophrenia. Markers of receptor/synaptic function and gene expression were most frequently differentially related to age in schizophrenia. Schizophrenia patients with greater disease severity and longer illness duration exhibited higher levels of inflammatory and oxidative stress biomarkers and shorter telomere length. Conclusions: Most studies show biomarker abnormalities in schizophrenia, and there is some suggestion for accelerated aging. Although definitive interpretation is limited by cross-sectional design of the published reports, findings in the area of gene expression and synaptic function are promising and pave the way for future longitudinal studies needed to fully test this hypothesis.

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“…Recently, telomere dysfunction in peripheral leukocytes has been described in psychiatric conditions. Accelerated telomere shortening and decreased telomerase activity has been reported in chronically stressed individuals (Epel et al, 2004), mood disorders (Simon et al, 2006), and schizophrenia Porton et al, 2008). Moreover, mouse TERT (mTERT)-deficient mice exhibited significantly altered anxiety-like behaviors (Lee et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

Hippocampal Telomerase Is Involved in the Modulation of Depressive Behaviors

Zhou¹,

Hu²,

Wu³

et al. 2011

J. Neurosci.

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Telomere and telomerase alterations have been reported in mood disorders. However, the role of telomerase in depression remains unclear. Here we show that chronic mild stress (CMS) led to a significant decrease in telomerase reverse transcriptase (TERT) level and telomerase activity in the hippocampus. Treatment with antidepressant fluoxetine reversed the CMS-induced TERT and telomerase activity changes. Inhibiting telomerase by systemic administration (100 mg ⅐ kg Ϫ1 ⅐ d Ϫ1 , i.p., for 14 d), intrahippocampal microinjection (0.7 mol, 2 l), or infusion (using an osmotic minipump, 0.134 g/l, 0.25 l/h) of 3Ј-azido-deoxythymidine (AZT) resulted in depression-like behaviors and impaired hippocampal neurogenesis in mice. In contrast, overexpressing telomerase by intrahippocampal infusion of recombinant adenovirus vector expressing mouse TERT (Ad-mTERT-GFP) led to neurogenesis upregulation, produced antidepressant-like behaviors, and prevented the CMS-induced behavioral modifications. Disrupting neurogenesis in the dentate gyrus by X-irradiation (15 Gy) of a restricted region of mouse brain containing the hippocampus abolished the antidepressant-like effect of Ad-mTERT-GFP. Additionally, AZT had no effect on DNA polymerase activity and did not cause cell damage in vitro and in vivo. Microinjection of AZT into the subventricular zone of lateral ventricle (0.7 mol, 2 l) inhibited local neurogenesis but had no behavioral effect. These results suggest that hippocampal telomerase is involved in the modulation of depression-related behaviors, possibly by regulating adult neurogenesis.

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Telomerase levels in schizophrenia: A preliminary study

Cited by 52 publications

References 37 publications

Cycloastragenol Is a Potent Telomerase Activator in Neuronal Cells: Implications for Depression Management

Cycloastragenol Is a Potent Telomerase Activator in Neuronal Cells: Implications for Depression Management

Systemic Biomarkers of Accelerated Aging in Schizophrenia: A Critical Review and Future Directions

Hippocampal Telomerase Is Involved in the Modulation of Depressive Behaviors

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