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

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.

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.

Metrics

  • 3,593
    views
  • 515
    downloads
  • 44
    citations

Views, downloads and citations are aggregated across all versions of this paper published by eLife.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  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
(2021)
Stimulus-induced gamma rhythms are weaker in human elderly with Mild Cognitive Impairment and Alzheimer's Disease
eLife 10:e61666.
https://doi.org/10.7554/eLife.61666

Share this article

https://doi.org/10.7554/eLife.61666

Further reading

    1. Medicine
    Pinanong Na-Phatthalung, Shumin Sun ... Fudi Wang
    Research Article

    The zinc transporter Slc30a1 plays an essential role in maintaining cellular zinc homeostasis. Despite this, its functional role in macrophages remains largely unknown. Here, we examine the function of Slc30a1 in host defense using mice models infected with an attenuated stain of Salmonella enterica Typhimurium and primary macrophages infected with the attenuated Salmonella. Bulk transcriptome sequencing in primary macrophages identifies Slc30a1 as a candidate in response to Salmonella infection. Whole-mount immunofluorescence and confocal microscopy imaging of primary macrophage and spleen from Salmonella-infected Slc30a1flag-EGFP mice demonstrate Slc30a1 expression is increased in infected macrophages with localization at the plasma membrane and in the cytosol. Lyz2-Cre-driven Slc30a1 conditional knockout mice (Slc30a1fl/fl;Lyz2-Cre) exhibit increased susceptibility to Salmonella infection compared to control littermates. We demonstrate that Slc30a1-deficient macrophages are defective in intracellular killing, which correlated with reduced activation of nuclear factor kappa B and reduction in nitric oxide (NO) production. Notably, the model exhibits intracellular zinc accumulation, demonstrating that Slc30a1 is required for zinc export. We thus conclude that zinc export enables the efficient NO-mediated antibacterial activity of macrophages to control invading Salmonella.

    1. Chromosomes and Gene Expression
    2. Medicine
    Xianghong Xie, Mingyue Gao ... Xiaojun Liu
    Research Article

    LncRNAs are involved in modulating the individual risk and the severity of progression in metabolic dysfunction-associated fatty liver disease (MASLD), but their precise roles remain largely unknown. This study aimed to investigate the role of lncRNA Snhg3 in the development and progression of MASLD, along with the underlying mechanisms. The result showed that Snhg3 was significantly downregulated in the liver of high-fat diet-induced obesity (DIO) mice. Notably, palmitic acid promoted the expression of Snhg3 and overexpression of Snhg3 increased lipid accumulation in primary hepatocytes. Furthermore, hepatocyte-specific Snhg3 deficiency decreased body and liver weight, alleviated hepatic steatosis and promoted hepatic fatty acid metabolism in DIO mice, whereas overexpression induced the opposite effect. Mechanistically, Snhg3 promoted the expression, stability and nuclear localization of SND1 protein via interacting with SND1, thereby inducing K63-linked ubiquitination modification of SND1. Moreover, Snhg3 decreased the H3K27me3 level and induced SND1-mediated chromatin loose remodeling, thus reducing H3K27me3 enrichment at the Pparg promoter and enhancing PPARγ expression. The administration of PPARγ antagonist T0070907 improved Snhg3-aggravated hepatic steatosis. Our study revealed a new signaling pathway, Snhg3/SND1/H3K27me3/PPARγ, responsible for mice MASLD and indicates that lncRNA-mediated epigenetic modification has a crucial role in the pathology of MASLD.