Increased brain vitamin D receptor expression and decreased expression of cathelicidin antimicrobial peptide in individuals who died by suicide

Postolache, Teodor T.; Akram, Faisal; Lee, Ellen; Lowry, Christopher A.; Stiller, John W.; Brenner, Lisa A.; Streeten, Elizabeth A.; Turecki, Gustavo; Dwivedi, Yogesh K.

doi:10.1016/j.jpsychires.2020.02.027

Cited by 8 publications

(14 citation statements)

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“…Behaviorally, in mice, psychological stress can reduce the expression of beta defensins in the skin, and depression can reduce alpha defensin expression in the intestine (Aberg et al, 2007 ; Suzuki et al, 2021 ). A postmortem study shows that human patients who died by suicide have decreased LL-37 expression in both dorsolateral prefrontal cortex and anterior cingulate cortex, which are critical for mood regulation (Bae et al, 2006 ), when compared to those who died by other causes (Postolache et al, 2020 ). Such evidence indicates an important correlation between AMPs and CNS functions in mammals, while it remains an area of investigation of whether they are parallel events or if there is a causal relationship.…”

Section: Amps and Nervous Systemmentioning

confidence: 99%

Regulatory Roles of Antimicrobial Peptides in the Nervous System: Implications for Neuronal Aging

Stuart

Franitza

Lezi

2022

Front. Cell. Neurosci.

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Antimicrobial peptides (AMPs) are classically known as important effector molecules in innate immunity across all multicellular organisms. However, emerging evidence begins to suggest multifunctional properties of AMPs beyond their antimicrobial activity, surprisingly including their roles in regulating neuronal function, such as sleep and memory formation. Aging, which is fundamental to neurodegeneration in both physiological and disease conditions, interestingly affects the expression pattern of many AMPs in an infection-independent manner. While it remains unclear whether these are coincidental events, or a mechanistic relationship exists, previous studies have suggested a close link between AMPs and a few key proteins involved in neurodegenerative diseases. This review discusses recent literature and advances in understanding the crosstalk between AMPs and the nervous system at both molecular and functional levels, with the aim to explore how AMPs may relate to neuronal vulnerability in aging.

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Section: Amps and Nervous Systemmentioning

confidence: 99%

Regulatory Roles of Antimicrobial Peptides in the Nervous System: Implications for Neuronal Aging

Stuart

Franitza

Lezi

2022

Front. Cell. Neurosci.

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“…Vitamin D receptors are located in areas of the brain involved in developing depression, including the hippocampus and hypothalamus [5,6]. Adjuvant treatment of depression with vitamin D supplementation has been recommended [9]. Risk of toxicity can be managed by monitoring as toxicity is typically symptomatic, including nausea and gastrointestinal symptoms, before proceeding to urinary tract stones.…”

Section: Plos Onementioning

confidence: 99%

“…A potential mechanism of action for vitamin D serum levels and suicide was found in a study of the post-mortem brain tissue from 15 depressed suicide decedents matched by age, sex, and death interval to 15 non-psychiatric controls [9]. Specifically, increased vitamin D receptor gene expression and decreased cathelicidin-related antimicrobial peptide expression were identified in the suicide decedents but not the matched controls.…”

Section: Introductionmentioning

confidence: 99%

“…A growing body of evidence has identified associations between suicidal behavior [3,[6][7][8][9][10][11][12][13] or depressive symptoms [14][15][16][17][18][19][20][21] and low levels of serum 25-hydroxyvitamin D (serum Vitamin D). In a case-control study of 495 service members who had been deployed and later died by suicide, those with seasonally-adjusted Vitamin D serum levels [ ]) less than 15.5 ng/mL had the highest risk of a suicide attempt [3].…”

Section: Introductionmentioning

confidence: 99%

“…Specifically, increased vitamin D receptor gene expression and decreased cathelicidin-related antimicrobial peptide expression were identified in the suicide decedents but not the matched controls. [9] However, randomized controlled trials of vitamin D supplementation and psychiatric outcomes have produced conflicting results, with trials reporting both positive [16,17,[19][20][21]23] and null or negative effects [14,15,18,[24][25][26]. The US Preventive Services Task Force reviewed 11 trials of Vitamin D supplementation and all-cause mortality but found no differences in mortality between the intervention and control groups in any study [27].…”

Section: Introductionmentioning

confidence: 99%

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The association between vitamin D serum levels, supplementation, and suicide attempts and intentional self-harm

Lavigne

Gibbons

2023

PLoS ONE

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Objectives The purpose of this study is to determine the associations between Vitamin D supplementation, 25(OH) blood serum levels, suicide attempts, and intentional self-harm in a population of veterans in the Department of Veterans Affairs (VA). Methods A retrospective cohort study of US Veterans supplemented with Vitamin D. Veterans with any Vitamin D3 (cholecalciferol) or Vitamin D2 (ergocalciferol) fill between 2010 and 2018 were matched 1:1 to untreated control veterans having similar demographics and medical histories. Cox proportional hazards regression was used to estimate the time from the first Vitamin D3 (cholecalciferol) or Vitamin D2 (ergocalciferol) prescription fill to the first suicide attempt or intentional self-harm. Analyses were repeated in stratified samples to measure associations by race (Black or White), gender (male or female), blood levels (0–19 ng/ml, 20–39 ng/ml, and 40+ ng/ml), and average daily dosage. Results Vitamin D3 and D2 supplementation were associated with a 45% and 48% lower risk of suicide attempt and self-harm ((D2 Hazard Ratio (HR) = 0.512, [95% CI, 0.457, 0.574]; D3 HR = 0.552, [95% CI, 0.511, 0.597])). Supplemented black veterans and veterans with 0–19 ng/ml vitamin D serum levels were at ~64% lower risk relative to controls (Black Veteran HR: 0.362 [95% CI: 0.298,0.440]; 0–19 ng/ml HR: 0.359 [95% CI: 0.215,0.598]). Supplementation with higher vitamin D dosages was associated with greater risk reductions than lower dosages (Log Average Dosage HR: 0.837 [95% CI: 0.779,0.900]). Conclusions Vitamin D supplementation was associated with a reduced risk of suicide attempt and self-harm in Veterans, especially in veterans with low blood serum levels and Black veterans.

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Alzheimer's disease as an innate autoimmune disease (AD²): A new molecular paradigm

Weaver

2022

Alzheimer's & Dementia

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A new model of Alzheimer's disease (AD) is presented: Alzheimer's disease as an autoimmune disease (AD 2 ). In response to pathogen-/damage-associated molecular pattern-stimulating events (e.g., infection, trauma, ischemia, pollution), amyloid beta (Aβ) is released as an early responder cytokine triggering an innate immunity cascade in which Aβ exhibits immunomodulatory/antimicrobial duality. However, Aβ's antimicrobial properties result in a misdirected attack upon "self" neurons, arising from the electrophysiological similarities between neurons and bacteria in terms of transmembrane potential gradients and anionic charges on outer membrane macromolecules. The subsequent breakdown products of necrotic neurons elicit further release of Aβ leading to a chronic, self-perpetuating cycle. In AD 2 , amino acid (trp, arg) metabolism is a central control player in modulating AD autoimmunity. AD 2 includes Aβ as an important molecular player, but rejects the "amyloid hypothesis," recognizing Aβ as a physiologically oligomerizing cytokine and part of a larger immunopathic conceptualization of AD.

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Increased brain vitamin D receptor expression and decreased expression of cathelicidin antimicrobial peptide in individuals who died by suicide

Cited by 8 publications

References 159 publications

Regulatory Roles of Antimicrobial Peptides in the Nervous System: Implications for Neuronal Aging

Regulatory Roles of Antimicrobial Peptides in the Nervous System: Implications for Neuronal Aging

The association between vitamin D serum levels, supplementation, and suicide attempts and intentional self-harm

Alzheimer's disease as an innate autoimmune disease (AD²): A new molecular paradigm

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Increased brain vitamin D receptor expression and decreased expression of cathelicidin antimicrobial peptide in individuals who died by suicide

Cited by 8 publications

References 159 publications

Regulatory Roles of Antimicrobial Peptides in the Nervous System: Implications for Neuronal Aging

Regulatory Roles of Antimicrobial Peptides in the Nervous System: Implications for Neuronal Aging

The association between vitamin D serum levels, supplementation, and suicide attempts and intentional self-harm

Alzheimer's disease as an innate autoimmune disease (AD2): A new molecular paradigm

Contact Info

Product

Resources

About

Alzheimer's disease as an innate autoimmune disease (AD²): A new molecular paradigm