BEHRENS PELLEGRINO, MARIA ISABEL
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BEHRENS PELLEGRINO, MARIA ISABEL
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BEHRENS PELLEGRINO, MARIA ISABEL
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mbehrens@udd.cl
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7007110355

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Senescence Markers in Peripheral Blood Mononuclear Cells in Amnestic Mild Cognitive Impairment and Alzheimer’s Disease

2022 , Felipe Salech , Carol D. SanMartín , Jorge Concha-Cerda , Esteban Romero-Hernández , Daniela P. Ponce , Gianella Liabeuf , Nicole K. Rogers , Paola Murgas , Bárbara Bruna , Jamileth More , BEHRENS PELLEGRINO, MARIA ISABEL

Recent studies suggest that cellular senescence plays a role in Alzheimer’s Disease (AD) pathogenesis. We hypothesize that cellular senescence markers might be tracked in the peripheral tissues of AD patients. Senescence hallmarks, including altered metabolism, cell-cycle arrest, DNA damage response (DDR) and senescence secretory associated phenotype (SASP), were measured in peripheral blood mononuclear cells (PBMCs) of healthy controls (HC), amnestic mild cognitive impairment (aMCI) and AD patients. Senescence-associated βeta-galactosidase (SA-β-Gal) activity, G0-G1 phase cell-cycle arrest, p16 and p53 were analyzed by flow cytometry, while IL-6 and IL-8 mRNA were analyzed by qPCR, and phosphorylated H2A histone family member X (γH2AX) was analyzed by immunofluorescence. Senescent cells in the brain tissue were determined with lipofuscin staining. An increase in the number of senescent cells was observed in the frontal cortex and hippocampus of advanced AD patients. PBMCs of aMCI patients, but not in AD, showed increased SA-β-Gal compared with HCs. aMCI PBMCs also had increased IL-6 and IL8 mRNA expression and number of cells arrested at G0-G1, which were absent in AD. Instead, AD PBMCs had significantly increased p16 and p53 expression and decreased γH2Ax activity compared with HC. This study reports that several markers of cellular senescence can be measured in PBMCs of aMCI and AD patients.

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Cancer History Avoids the Increase of Senescence Markers in Peripheral Cells of Amnestic Mild Cognitive Impaired Patients

2023 , Carol D. SanMartín , Felipe Salech , Daniela Paz Ponce , Jorge Concha-Cerda , Esteban Romero-Hernández , Gianella Liabeuf , Nicole K. Rogers , Paola Murgas , Bárbara Bruna , Jamileth More , BEHRENS PELLEGRINO, MARIA ISABEL

Epidemiological studies show that having a history of cancer protects from the development of Alzheimer’s Disease (AD), and vice versa, AD protects from cancer. The mechanism of this mutual protection is unknown. We have reported that the peripheral blood mononuclear cells (PBMC) of amnestic cognitive impairment (aMCI) and Alzheimer’s Disease (AD) patients have increased susceptibility to oxidative cell death compared to control subjects, and from the opposite standpoint a cancer history is associated with increased resistance to oxidative stress cell death in PBMCs, even in those subjects who have cancer history and aMCI (Ca + aMCI). Cellular senescence is a regulator of susceptibility to cell death and has been related to the pathophysiology of AD and cancer. Recently, we showed that cellular senescence markers can be tracked in PBMCs of aMCI patients, so we here investigated whether these senescence markers are dependent on having a history of cancer. Senescence-associated βeta-galactosidase (SA-β-Gal) activity, G0-G1 phase cell-cycle arrest, p16 and p53 were analyzed by flow cytometry; phosphorylated H2A histone family member X (γH2AX) by immunofluorescence; IL-6 and IL-8 mRNA by qPCR; and plasmatic levels by ELISA. Senescence markers that were elevated in PBMCs of aMCI patients, such as SA-β-Gal, Go-G1 arrested cells, IL-6 and IL-8 mRNA expression, and IL-8 plasmatic levels, were decreased in PBMCs of Ca + aMCI patients to levels similar to those of controls or of cancer survivors without cognitive impairment, suggesting that cancer in the past leaves a fingerprint that can be peripherally traceable in PBMC samples. These results support the hypothesis that the senescence process might be involved in the inverse association between cancer and AD.

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Inverse Relationship Between Alzheimer's Disease and Cancer: How Immune Checkpoints Might Explain the Mechanisms Underlying Age-Related Diseases.

2019 , Nicole K. Rogers , Cesar Romero , Carol D. SanMartín , Daniela P. Ponce , Felipe Salech , Mercedes N. López , Alejandra Gleisner , Fabián Tempio , BEHRENS PELLEGRINO, MARIA ISABEL

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Frizzled-1 receptor regulates adult hippocampal neurogenesis

2016 , Muriel D. Mardones , Gabriela A. Andaur , Manuel Varas-Godoy , Jenny F. Henriquez , Felipe Salech , BEHRENS PELLEGRINO, MARIA ISABEL , Andrés Couve , Nibaldo C. Inestrosa , Lorena Varela-Nallar

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Nicotinamide, a Poly [ADP-Ribose] Polymerase 1 (PARP-1) Inhibitor, as an Adjunctive Therapy for the Treatment of Alzheimer’s Disease

2020 , Felipe Salech , Daniela P. Ponce , Andrea C. Paula-Lima , Carol D. SanMartin , BEHRENS PELLEGRINO, MARIA ISABEL

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Local Klotho Enhances Neuronal Progenitor Proliferation in the Adult Hippocampus

2017 , Felipe Salech , Lorena Varela-Nallar , Sebastián B Arredondo , Daniel B Bustamante , Gabriela A Andaur , Rodrigo Cisneros , Daniela P Ponce , Patricia Ayala , Nibaldo C Inestrosa , José L Valdés , BEHRENS PELLEGRINO, MARIA ISABEL , Andrés Couve

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Vitamin D Increases Aβ140 Plasma Levels and Protects Lymphocytes from Oxidative Death in Mild Cognitive Impairment Patients

2018 , Carol D. SanMartín , Mauricio Henriquez , Carlos Chacon , Daniela P. Ponce , Felipe Salech , Nicole K. Rogers , BEHRENS PELLEGRINO, MARIA ISABEL

Background: Mild cognitive impairment (MCI) has an increased rate of progression to dementia. Alterations of some metabolic factors, such as deficiency of vitamin D, are a risk factor for cognitive deterioration. Vitamin D is involved in the clearance of β-amyloid (Aβ) from the brain. We have reported that lymphocytes from Alzheimer's disease (AD) patients have an increased susceptibility to oxidative death by H2O2 exposure, but currently it is unknown if this characteristic is modifiable in vivo. Objective: To determine if correction of low vitamin D levels protects lymphocytes from oxidative death and increases Aβ1-40 plasma levels in MCI and very early AD (VEAD) patients. Method: Sixteen MCI, 11 VEAD and 25 healthy control (HC) voluntaries were evaluated with the Clinical Dementia Rating (CDR), Montreal Cognitive assessment (MoCA), and Memory Index score (MIS). Lymphocyte death was measured by flow cytometry after 20h exposure to H2O2. In patients with low levels of vitamin D -11 MCI, 9 VEAD and 20 HC- lymphocyte H2O2-death, plasma Aβ1-40 levels and cognitive status were evaluated pre- and post-vitamin D supplementation for 6 months. Results: Lymphocytes from MCI and VEAD patients showed increased susceptibility to oxidative death at study entry. In MCI, but not VEAD patients, lymphocyte susceptibility to death and Aβ1-40 levels plasma levels improved after 6 months of vitamin D supplementation. In addition, cognitive status on follow-up (18 months) improved in MCI patients after vitamin D supplementation. Conclusion: Vitamin D supplementation may be beneficial in MCI. The lack of effect in VEAD may be due to a more advanced stage or different characteristics of the neurodegenerative process.

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