1. Medicine
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Stimulus-induced gamma rhythms are weaker in human elderly with Mild Cognitive Impairment and Alzheimer's Disease

  1. Dinavahi VPS Murty
  2. Keerthana Manikandan
  3. Wupadrasta Santosh Kumar
  4. Ranjini Garani Ramesh
  5. Simran Purokayastha
  6. Bhargavi Nagendra
  7. Abhishek M. L.
  8. Aditi Balakrishnan
  9. Mahendra Javali
  10. Naren Prahalada Rao
  11. Supratim Ray  Is a corresponding author
  1. Indian Institute of Science, India
  2. MS Ramaiah Medical College & Memorial Hospital, India
  3. National Institute of Mental Health and Neurosciences, India
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Cite this article as: eLife 2021;10:e61666 doi: 10.7554/eLife.61666

Abstract

Alzheimer's Disease (AD) in elderly adds substantially to socio-economic burden necessitating early diagnosis. While recent studies in rodent models of AD have suggested diagnostic and therapeutic value for gamma rhythms in brain, the same has not been rigorously tested in humans. In this case-control study, we recruited a large population (N=244; 106 females) of elderly (>49 years) subjects from the community, who viewed large gratings that induced strong gamma oscillations in their electroencephalogram (EEG). These subjects were classified as healthy (N=227), mild-cognitively-impaired (MCI; N=12) or AD (N=5) based on clinical history and Clinical Dementia Rating scores. Surprisingly, stimulus-induced gamma rhythms, but not alpha or steady-state visually evoked responses, were significantly lower in MCI/AD subjects compared to their age and gender matched controls. This reduction was not due to differences in eye-movements or baseline power. Our results suggest that gamma could be used as potential screening tool for MCI/AD in humans.

Data availability

All spectral analyses were performed using Chronux toolbox (version 2.10), available at http://chronux.org. Relevant data and codes are available at the following GitHub repository: https://github.com/supratimray/TLSAEEGProjectPrograms.

Article and author information

Author details

  1. Dinavahi VPS Murty

    Centre for Neuroscience, Indian Institute of Science, Bengaluru, India
    Competing interests
    The authors declare that no competing interests exist.
  2. Keerthana Manikandan

    Centre for Neuroscience, Indian Institute of Science, Bengaluru, India
    Competing interests
    The authors declare that no competing interests exist.
  3. Wupadrasta Santosh Kumar

    Centre for Neuroscience, Indian Institute of Science, Bengaluru, India
    Competing interests
    The authors declare that no competing interests exist.
  4. Ranjini Garani Ramesh

    Centre for Neuroscience, Indian Institute of Science, Bengaluru, India
    Competing interests
    The authors declare that no competing interests exist.
  5. Simran Purokayastha

    Centre for Neuroscience, Indian Institute of Science, Bengaluru, India
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6096-1477
  6. Bhargavi Nagendra

    Centre for Neuroscience, Indian Institute of Science, Bengaluru, India
    Competing interests
    The authors declare that no competing interests exist.
  7. Abhishek M. L.

    Centre for Neuroscience, Indian Institute of Science, Bengaluru, India
    Competing interests
    The authors declare that no competing interests exist.
  8. Aditi Balakrishnan

    Centre for Neuroscience, Indian Institute of Science, Bengaluru, India
    Competing interests
    The authors declare that no competing interests exist.
  9. Mahendra Javali

    Department of Neurology, MS Ramaiah Medical College & Memorial Hospital, Bangalore, India
    Competing interests
    The authors declare that no competing interests exist.
  10. Naren Prahalada Rao

    Department of Psychiatry, National Institute of Mental Health and Neurosciences, Bangalore, India
    Competing interests
    The authors declare that no competing interests exist.
  11. Supratim Ray

    Centre for Neuroscience, Indian Institute of Science, Bengaluru, India
    For correspondence
    sray@iisc.ac.in
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1968-1382

Funding

Tata Trusts

  • Naren Prahalada Rao
  • Supratim Ray

Wellcome Trust/DBT India Alliance (Intermediate fellowship 500145/Z/09/Z)

  • Supratim Ray

Wellcome Trust/DBT India Alliance (Senior fellowship IA/S/18/2/504003)

  • Supratim Ray

Department of Biotechnology, Ministry of Science and Technology, India (DBT-IISc Partnership Programme)

  • Supratim Ray

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Human subjects: We obtained informed consent from all participants before the experiment. The Institute Human Ethics Committees of Indian Institute of Science (IHEC numbers: original: 22/2014, revised: 7-15092017), NIMHANS, and M S Ramaiah Hospital, Bangalore approved all procedures.

Reviewing Editor

  1. Martin Vinck, Ernst Strüngmann Institute (ESI) for Neuroscience in Cooperation with Max Planck Society, Germany

Publication history

  1. Received: July 31, 2020
  2. Accepted: May 23, 2021
  3. Accepted Manuscript published: June 8, 2021 (version 1)

Copyright

© 2021, Murty et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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    Vaccine hesitancy can limit the benefits of available vaccines in halting the spread of COVID-19 pandemic. Previously published studies paid little attention to Arab countries, which has a population of over 440 million. In this study, we present the results of the first large-scale multinational study that measures vaccine hesitancy among Arab-speaking subjects.

    Methods:

    An online survey in Arabic was conducted from 14 January 2021 to 29 January 2021. It consisted of 17 questions capturing demographic data, acceptance of COVID-19 vaccine, attitudes toward the need for COVID-19 vaccination and associated health policies, and reasons for vaccination hesitancy. R software v.4.0.2 was used for data analysis and visualization.

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    Our results show higher vaccine hesitancy and refusal among Arab subjects, related mainly to distrust and concerns about side effects. Health authorities and Arab scientific community have to transparently address these concerns to improve vaccine acceptance.

    Funding:

    This study received no funding.

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    Erythroblast erythroferrone (ERFE) secretion inhibits hepcidin expression by sequestering several bone morphogenetic protein (BMP) family members to increase iron availability for erythropoiesis.

    Methods:

    To address whether ERFE functions also in bone and whether the mechanism of ERFE action in bone involves BMPs, we utilize the Erfe-/- mouse model as well as β–thalassemic (Hbbth3/+) mice with systemic loss of ERFE expression. In additional, we employ comprehensive skeletal phenotyping analyses as well as functional assays in vitro to address mechanistically the function of ERFE in bone.

    Results:

    We report that ERFE expression in osteoblasts is higher compared with erythroblasts, is independent of erythropoietin, and functional in suppressing hepatocyte hepcidin expression. Erfe-/- mice display low–bone–mass arising from increased bone resorption despite a concomitant increase in bone formation. Consistently, Erfe-/- osteoblasts exhibit enhanced mineralization, Sost and Rankl expression, and BMP–mediated signaling ex vivo. The ERFE effect on osteoclasts is mediated through increased osteoblastic RANKL and sclerostin expression, increasing osteoclastogenesis in Erfe-/- mice. Importantly, Erfe loss in Hbbth3/+mice, a disease model with increased ERFE expression, triggers profound osteoclastic bone resorption and bone loss.

    Conclusions:

    Together, ERFE exerts an osteoprotective effect by modulating BMP signaling in osteoblasts, decreasing RANKL production to limit osteoclastogenesis, and prevents excessive bone loss during expanded erythropoiesis in β–thalassemia.

    Funding:

    YZG acknowledges the support of the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (R01 DK107670 to YZG and DK095112 to RF, SR, and YZG). MZ acknowledges the support of the National Institute on Aging (U19 AG60917) and NIDDK (R01 DK113627). TY acknowledges the support of the National Institute on Aging (R01 AG71870). SR acknowledges the support of NIDDK (R01 DK090554) and Commonwealth Universal Research Enhancement (CURE) Program Pennsylvania.