New Evidence on Iron, Copper Accumulation and Zinc Depletion and Its Correlation with DNA Integrity in Aging Human Brain Regions

By Vasudevaraju, P.; Bharathi et al. | Indian Journal of Psychiatry, April-June 2010 | Go to article overview

New Evidence on Iron, Copper Accumulation and Zinc Depletion and Its Correlation with DNA Integrity in Aging Human Brain Regions


Vasudevaraju, P., Bharathi, Jyothsna, T., Shamasundar, N., Rao, Subba, Balaraj, B., Rao, Ksj, Rao, T. Sathyanarayana, Indian Journal of Psychiatry


Byline: P. Vasudevaraju, Bharathi, T. Jyothsna, N. Shamasundar, Subba. Rao, B. Balaraj, KSJ. Rao, T. Sathyanarayana Rao

Deoxyribonucleic acid (DNA) conformation and stability play an important role in brain function. Earlier studies reported alterations in DNA integrity in the brain regions of neurological disorders like Parkinson's and Alzheimer's diseases. However, there are only limited studies on DNA stability in an aging brain and the factors responsible for genomic instability are still not clear. In this study, we assess the levels of Copper (Cu), Iron (Fe) and Zinc (Zn) in three age groups (Group I: below 40 years), Group II: between 41-60 years) and Group III: above 61 years) in hippocampus and frontal cortex regions of normal brains. The number of samples in each group was eight. Genomic DNA was isolated and DNA integrity was studied by nick translation studies and presented as single and double strand breaks. The number of single strand breaks correspondingly increased with aging compared to double strand breaks. The strand breaks were more in frontal cortex compared to hippocampus. We observed that the levels of Cu and Fe are significantly elevated while Zn is significantly depleted as one progresses from Group I to Group III, indicating changes with aging in frontal cortex and hippocampus. But the elevation of metals was more in frontal cortical region compared to hippocampal region. There was a clear correlation between Cu and Fe levels versus strand breaks in aging brain regions. This indicates that genomic instability is progressive with aging and this will alter the gene expressions. To our knowledge, this is a new comprehensive database to date, looking at the levels of redox metals and corresponding strand breaks in DNA in two brain regions of the aging brain. The biological significance of these findings with relevance to mental health will be discussed.

Introduction

The failure in normal healthy aging leads to mental disorders in aged population.[sup] [1] Bipolar disorder (BD) is a major geriatric mental health problem. It affects about 1% of the population and causes severe neuropsychological impairments and has been implicated in functional impairment.[sup] [2] What we mean by normal and healthy aging and for that matter what are the triggering risk factors for geriatric mental health problems are still puzzling. To understand this better, we need to explore the biology of aging properly. Both structural, chemical, functional brain imaging using magnetic resonance imaging and postmortem studies have demonstrated volume loss in brain in subjects with BD and also with aging.[sup] [3],[4],[5],[6] Recent postmortem studies in BD have demonstrated reductions in number and density of nerve cells, as well as changes in cell body size and shape of neurons and glia, implicating specific cell pathology in the mood disorders and control aged brains.[sup] [4]

These studies give an insight into the central role played by neuronal cell death in the pathology of psychiatric disorders and is absent in normal healthy aging. The major risk factors implicated in age related disorders, is the elevation in oxidative stress and failure in antioxidant mechanisms.[sup] [7],[8],[9],[10],[11],[12] The oxidative stress phenomenon leads to DNA instability and gene expression failure in normal aging. Does the failure in repair mechanism lead to neuropsychiatric problems? The data base on this aspect is limited. A dysregulation in apoptotic mechanism is believed to play a role in a variety of neuropsychiatric disorders.[sup] [13],[14],[15],[16],[17],[18],[19] Further, DNA fragmentations have been well shown to be associated with neurodegenerative disorders like Parkinson disease (PD).[sup] [20],[21],[22],[23] The current study aims to assess the genomic integrity in terms of DNA fragmentation and its relation to the levels of redox active metals in frontal cortex and hippocampal brain regions of different age groups and to ascertain whether altered genome integrity plays a role in geriatric psychiatric disorders. …

The rest of this article is only available to active members of Questia

Already a member? Log in now.

Notes for this article

Add a new note
If you are trying to select text to create highlights or citations, remember that you must now click or tap on the first word, and then click or tap on the last word.
One moment ...
Default project is now your active project.
Project items
Notes
Cite this article

Cited article

Style
Citations are available only to our active members.
Buy instant access to cite pages or passages in MLA 8, MLA 7, APA and Chicago citation styles.

(Einhorn, 1992, p. 25)

(Einhorn 25)

(Einhorn 25)

1. Lois J. Einhorn, Abraham Lincoln, the Orator: Penetrating the Lincoln Legend (Westport, CT: Greenwood Press, 1992), 25, http://www.questia.com/read/27419298.

Note: primary sources have slightly different requirements for citation. Please see these guidelines for more information.

Cited article

New Evidence on Iron, Copper Accumulation and Zinc Depletion and Its Correlation with DNA Integrity in Aging Human Brain Regions
Settings

Settings

Typeface
Text size Smaller Larger Reset View mode
Search within

Search within this article

Look up

Look up a word

  • Dictionary
  • Thesaurus
Please submit a word or phrase above.
Print this page

Print this page

Why can't I print more than one page at a time?

Help
Full screen
Items saved from this article
  • Highlights & Notes
  • Citations
Some of your highlights are legacy items.

Highlights saved before July 30, 2012 will not be displayed on their respective source pages.

You can easily re-create the highlights by opening the book page or article, selecting the text, and clicking “Highlight.”

matching results for page

    Questia reader help

    How to highlight and cite specific passages

    1. Click or tap the first word you want to select.
    2. Click or tap the last word you want to select, and you’ll see everything in between get selected.
    3. You’ll then get a menu of options like creating a highlight or a citation from that passage of text.

    OK, got it!

    Cited passage

    Style
    Citations are available only to our active members.
    Buy instant access to cite pages or passages in MLA 8, MLA 7, APA and Chicago citation styles.

    "Portraying himself as an honest, ordinary person helped Lincoln identify with his audiences." (Einhorn, 1992, p. 25).

    "Portraying himself as an honest, ordinary person helped Lincoln identify with his audiences." (Einhorn 25)

    "Portraying himself as an honest, ordinary person helped Lincoln identify with his audiences." (Einhorn 25)

    "Portraying himself as an honest, ordinary person helped Lincoln identify with his audiences."1

    1. Lois J. Einhorn, Abraham Lincoln, the Orator: Penetrating the Lincoln Legend (Westport, CT: Greenwood Press, 1992), 25, http://www.questia.com/read/27419298.

    Cited passage

    Thanks for trying Questia!

    Please continue trying out our research tools, but please note, full functionality is available only to our active members.

    Your work will be lost once you leave this Web page.

    Buy instant access to save your work.

    Already a member? Log in now.

    Search by... Author
    Show... All Results Primary Sources Peer-reviewed

    Oops!

    An unknown error has occurred. Please click the button below to reload the page. If the problem persists, please try again in a little while.