Skip to main content
Advertisement

Main menu

  • Home
  • Articles
    • Current Issue
    • Fast Forward
    • Latest Articles
    • Archive
  • Information
    • Instructions to Authors
    • Submit a Manuscript
    • FAQs
    • For Subscribers
    • Terms & Conditions of Use
    • Permissions
  • Editorial Board
  • Alerts
    • Alerts
    • RSS Feeds
  • Virtual Issues
  • Feedback
  • Submit
  • Other Publications
    • Drug Metabolism and Disposition
    • Journal of Pharmacology and Experimental Therapeutics
    • Molecular Pharmacology
    • Pharmacological Reviews
    • Pharmacology Research & Perspectives
    • ASPET

User menu

  • My alerts
  • Log in
  • My Cart

Search

  • Advanced search
Pharmacological Reviews
  • Other Publications
    • Drug Metabolism and Disposition
    • Journal of Pharmacology and Experimental Therapeutics
    • Molecular Pharmacology
    • Pharmacological Reviews
    • Pharmacology Research & Perspectives
    • ASPET
  • My alerts
  • Log in
  • My Cart
Pharmacological Reviews

Advanced Search

  • Home
  • Articles
    • Current Issue
    • Fast Forward
    • Latest Articles
    • Archive
  • Information
    • Instructions to Authors
    • Submit a Manuscript
    • FAQs
    • For Subscribers
    • Terms & Conditions of Use
    • Permissions
  • Editorial Board
  • Alerts
    • Alerts
    • RSS Feeds
  • Virtual Issues
  • Feedback
  • Submit
  • Visit Pharm Rev on Facebook
  • Follow Pharm Rev on Twitter
  • Follow ASPET on LinkedIn
Review ArticleReview Article

Vitamin D and Depression: Cellular and Regulatory Mechanisms

Michael J. Berridge
Eric L. Barker, ASSOCIATE EDITOR
Pharmacological Reviews April 2017, 69 (2) 80-92; DOI: https://doi.org/10.1124/pr.116.013227
Michael J. Berridge
Emeritus Babraham Fellow, The Babraham Institute, Cambridge, United Kingdom
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Eric L. Barker
Emeritus Babraham Fellow, The Babraham Institute, Cambridge, United Kingdom
Roles: ASSOCIATE EDITOR
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Article
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF
Loading

Article Figures & Data

Figures

  • Fig. 1.
    • Download figure
    • Open in new tab
    • Download powerpoint
    Fig. 1.

    The role of Ca2+ signaling in depression. Increased glutamate that occurs during depression enhances Ca2+ through the activation of NMDAR Ca2+ channels and by activation of the metabotropic glutamatergic receptor 5 (mGluR5) that is coupled to phospholipase C (PLC) to hydrolyze phosphatidylinositol 4,5-bisphosphate (PtdIns4,5P2) to form inositol 1,4,5-trisphosphate (InsP3) that releases Ca2+ from the endoplasmic reticulum (ER). Acetylcholine acting through the muscarinic 1 (M1) receptor also stimulates the formation of InsP3. The hydrolysis of PIP2, which normally acts to open the Kv7 2/3 channels that hyperpolarizes the neuronal membrane, acts to close these K+ channels and the membrane depolarizes, resulting in enhanced neuronal excitability. Vitamin D acts to reduce Ca2+ signaling by acting through the vitamin D receptor (VDR) to increase the expression of the Ca2+ buffer calbindin and it increases expression of the plasma membrane Ca2+ pump (PMCA) and the sodium/Ca2+ exchanger 1 (NCX1). Vitamin D also reduces the level of Ca2+ by reducing the expression of the L-type CaV1.2 channel.

  • Fig. 2.
    • Download figure
    • Open in new tab
    • Download powerpoint
    Fig. 2.

    Vitamin D prevents the onset of depression by activating a number of processes that are critical to maintain normal healthy neurons. Vitamin D enters the nucleus where it associates with the retinoid X receptor (RXR) and then binds to the vitamin D response element (VDRE), which is located on a large number of genes. It maintains Ca2+ homeostasis by inducing the expression of calbindin, parvalbumin, Na+/Ca2+ exchanger 1 (NCX1), and the plasma membrane Ca2+-ATPase (PMCA) pump. It also regulates Ca2+ by reducing the expression of the CaV1.2 calcium channel. It activates expression of many antioxidant genes such as the nuclear factor-erythroid-2-related factor 2 (NRF2), γ-glutamyl transpeptidase (γ-GT), glutamate cysteine ligase (GCLC), glutathione reductase (GR), glutathione peroxidase (Gpx). It controls the formation of serotonin by increasing the level of tryptophan hydroxylase 2 (TPH2) while repressing tryptophan hydroxylase1 (TPH1). It reduces inflammation by reducing the expression of inflammatory cytokines. It regulates the expression of many mitochondrial proteins that maintain normal mitochondrial respiration. Finally, it regulates the epigenetic landscape by promoting the expression of DNA demethylases such as Jumonji domain-containing protein 1A and 3 (JMJD1A, JMJD3) and lysine-specific demethylase 1 and 2 (LSD1, LSD2).

PreviousNext
Back to top

In this issue

Pharmacological Reviews: 69 (2)
Pharmacological Reviews
Vol. 69, Issue 2
1 Apr 2017
  • Table of Contents
  • Table of Contents (PDF)
  • About the Cover
  • Index by author
  • Editorial Board (PDF)
  • Front Matter (PDF)
Download PDF
Article Alerts
Sign In to Email Alerts with your Email Address
Email Article

Thank you for sharing this Pharmacological Reviews article.

NOTE: We request your email address only to inform the recipient that it was you who recommended this article, and that it is not junk mail. We do not retain these email addresses.

Enter multiple addresses on separate lines or separate them with commas.
Vitamin D and Depression: Cellular and Regulatory Mechanisms
(Your Name) has forwarded a page to you from Pharmacological Reviews
(Your Name) thought you would be interested in this article in Pharmacological Reviews.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
Review ArticleReview Article

Vitamin D and Depression

Michael J. Berridge
Pharmacological Reviews April 1, 2017, 69 (2) 80-92; DOI: https://doi.org/10.1124/pr.116.013227

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero

Share
Review ArticleReview Article

Vitamin D and Depression

Michael J. Berridge
Pharmacological Reviews April 1, 2017, 69 (2) 80-92; DOI: https://doi.org/10.1124/pr.116.013227
del.icio.us logo Digg logo Reddit logo Twitter logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
    • Abstract
    • I. Introduction
    • II. Dysfunctional Neural Circuits in Depression
    • III. Tonic Excitatory Drive and Depression
    • IV. Enhanced Neuronal Ca2+ Signaling in Depression
    • V. Inflammation and Depression
    • VI. Vitamin D and Depression
    • VII. Depression and Alzheimer’s Disease
    • VIII. Conclusion
    • Authorship Contributions
    • Footnotes
    • Abbreviations
    • References
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • Structure and Inhibition of NLRP3 Inflammasome
  • Neural mechanisms of general anesthesia
  • Systems pharmacology in drug-induced mitochondrial toxicity
Show more Review Articles

Similar Articles

Advertisement
  • Home
  • Alerts
Facebook   Twitter   LinkedIn   RSS

Navigate

  • Current Issue
  • Latest Articles
  • Archive
  • Search for Articles
  • Feedback
  • ASPET

More Information

  • About Pharmacological Reviews
  • Editorial Board
  • Instructions to Authors
  • Submit a Manuscript
  • Customized Alerts
  • RSS Feeds
  • Subscriptions
  • Permissions
  • Terms & Conditions of Use

ASPET's Other Journals

  • Drug Metabolism and Disposition
  • Journal of Pharmacology and Experimental Therapeutics
  • Molecular Pharmacology
  • Pharmacology Research & Perspectives
ISSN 1521-0081 (Online)

Copyright © 2023 by the American Society for Pharmacology and Experimental Therapeutics