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Nerve cells and Vitamin D – many studies

Vitamin D: The crucial neuroprotective factor for nerve cells - Sept 2024

Neuroscience 27 Sept 2024 https://doi.org/10.1016/j.neuroscience.2024.09.042 entire PDF behind a paywall
Yuxin Shi a b d 1, Yuchen Shi a b d 1, Rao Jie a, Jiawei He a b d, Zhaohui Luo a b c d, Jing Li a b d

Highlights_

  • Vitamin D plays an important role in the nervous system.
  • Vitamin D acts on neurons and glial cells in the central nervous system.
  • The occurrence of many neuropsychiatric diseases may also be related to abnormal brain function and neurological function caused by vitamin D deficiency.

Abstract
Vitamin D is well known for its role in regulating the absorption and utilization of calcium and phosphorus as well as bone formation, and a growing number of studies have shown that vitamin D also has important roles in the nervous system, such as maintaining neurological homeostasis and protecting normal brain function, and that neurons and glial cells may be the targets of these effects. Most reviews of vitamin D’s effects on the nervous system have focused on its overall effects, without distinguishing the contributors to these effects. In this review, we mainly focus on the cells of the central nervous system, summarizing the effects of vitamin D on them and the related pathways. With this review, we hope to elucidate the role of vitamin D in the nervous system at the cellular level and provide new insights into the prevention and treatment of neurodegenerative diseases in the direction of neuroprotection, myelin regeneration, and so on.

Introduction
Cells in the nervous system consist of neurons and glial cells. Neurons are the most basic structural and functional units of the nervous system, capable of receiving, integrating, and transmitting information. Recent studies have shown that the number of glial cells is roughly equal to that of neurons, and they play an important role in the maintenance of the homeostasis of the nervous system. There are three main types of glial cells in the central nervous system(CNS), which are oligodendrocytes, astrocytes, and microglial cells in descending order of their amount (von Bartheld et al., 2016). Over the past few decades, a large number of studies have demonstrated the significant effects of various vitamins on these cells, most notably vitamin D.

Vitamin D is a fat-soluble vitamin that is involved in the regulation of calcium and phosphorus metabolism in the body as a sterol derivative. Vitamin D is either obtained from the diet (including vitamin D2 from plant sources and vitamin D3 from animal sources) or synthesized in the body from 7-dehydrocholesterol. Vitamin D is biologically active after two hydroxylations, i.e., 25-hydroxyvitamin D catalyzed by 25-hydroxylase (CYP2R1) in the liver and 1,25-dihydroxyvitamin D catalyzed by 1alpha-hydroxylase (CYP27B1) in the kidneys, and it exerts its effects through its action in organs and tissues, such as the small intestine, bone, and the kidneys (Dixon and Mason, 2009). The breakdown of vitamin D is catalyzed by the enzyme 24-hydroxylase (CYP24A1), which breaks down 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D to the biologically inactive 24,25-dihydroxyvitamin D and 1,24,25-trihydroxyvitamin D, respectively (Jones et al., 2012).

There is growing evidence suggesting that vitamin D plays many roles in the nervous system in addition to its classically believed role in calcium and phosphorus metabolism. Altered vitamin D status has been shown to affect biological processes such as cytokine release, cell differentiation, protein expression, signaling, neurotransmitter release, and other biological processes in the nervous system (Cui and Eyles, 2022); which play a role in neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and multiple sclerosis, and the use of vitamin D as a supplement has been shown to have a positive effect in several neurodegenerative diseases (Wang et al., 2023, Lasoń, 2023). Studies have shown that the central nervous system is an important target organ for vitamin D, and vitamin D receptors are widely distributed in the cerebral cortex, substantia nigra, hippocampus, amygdala, thalamus, and hypothalamus of adults (Cui, 2013), and are mainly located in the nuclei of neurons and glia. Various cells in the central nervous system express either a nuclear receptor, the vitamin D receptor (VDR), or a membrane receptor, protein disulfide isomerase A3 (PDIA3), in response to vitamin D signaling (Landel, 2018), a response that may involve the activation of signaling molecules such as phospholipase A2 (PLA2) and c-Src (Chen, 2013). In addition to this, some of these cells can synthesize and catabolize vitamin D via CYP27B1 and CYP24A1 (Landel, 2018), and vitamin D stimulation also affects the levels of the above enzymes, altering local vitamin D metabolism (Smolders, 2013). Consequently, these cells may mediate the effects of vitamin D on the nervous system as described above. (Fig. 1).

In addition, vitamin D acts on a variety of immune-related cells of the nervous system, such as microglia and astrocytes (Menéndez and Manucha, 2024). On the one hand, these cells are an important part of the structure and function of the nervous system, and on the other hand, these cells also play an important role in regulating the immune microenvironment of the nervous system. Astrocytes and microglia also mediate interactions between the immune system and the CNS (Jo, 2015). Vitamin D promotes microglia to sense environmental changes, respond to noxious stimuli, and engulf debris and apoptotic neurons. In addition, vitamin D promotes the release of soluble factors from microglia as well as astrocytes that inhibit neuroinflammation (Menéndez and Manucha, 2024). Thus regulating the neuroimmune microenvironment.

Considering that nerve cells play an important role in a variety of neurodegenerative diseases, vitamin D can affect the nervous system through nerve cells (Lasoń, 2023). In this review, we discuss the effects of vitamin D on different nerve cells in the central nervous system and its related pathways of action and explore the possibility of improving the function of nerve cells through vitamin D supplementation as a means of alleviating patients' symptoms and improving their prognosis. From the perspective of different nerve cells, we intend to provide some insights into the future treatment of neurodegenerative diseases.

Section snippets
Effects of vitamin D on neuron
Studies have shown that vitamin D may play an important role in neuronal activity, affecting normal physiological functions such as differentiation, maturation, and death of neurons, and that its sites of action include synapses, neurites, and others.
Effects of vitamin D on microglia and the neuroimmune environment…

Neuroinflammation is a basic immune response characterized by increased glial cell activation, increased secretion of pro-inflammatory cytokines, altered blood–brain barrier permeability, and peripheral leukocyte invasion to protect the brain from injury….

Microglia, as important immune cells in the central nervous system, are involved in neuroinflammatory responses. Unlike other cells in the central nervous system, microglia and peripheral macrophages share a common origin and have a strong…

Effects of vitamin D on astrocyte and the neuroimmune environment…
Astrocytes are the most abundant glial cells in the central nervous system (CNS), where they perform a wide range of homeostatic functions, such as providing support to other CNS resident cells by buffering excess neurotransmitters and regulating synaptic and blood–brain barrier (BBB) functions (Endo, 2022). Astrocytes also play a variety of roles in CNS inflammation (Giovannoni and Quintana, 2020).
Stimulates by a variety of pro-inflammatory factors, such as inflammatory cytokines TNF-α, IL-1b…

Effects of vitamin D on oligodendrocyte
Promoting myelin repair and regeneration has been shown to be the most significant effect of vitamin D on oligodendrocytes (Gomez-Pinedo, 2020), and the great potential of vitamin D to regulate oligodendrocyte function has been demonstrated by researches related to their ferroptosis (Cai, 2022)….

Vitamin D and neurological disorders
In recent years, the role of vitamin D in brain development and nervous system development and function has been gradually confirmed by a large number of studies. In addition to the direct effects on various nerve cells mentioned above, vitamin D is also closely related to the permeability and integrity of the blood–brain barrier (BBB) (de Oliveira, 2020). Studies have shown that VDR-deficient microglia are more pro-inflammatory and secrete more TNF-α and IFN-γ. These inflammatory cytokines…

Future perspectives
From the above studies, it can be seen that in all types of cells in the central nervous system, vitamin D can ultimately improve the cell survival state and the ability to cope with external stimuli through a variety of pathways, including the reduction of neuroinflammation, the decrease of oxidative stress, and the increase of neurotrophic factors, thus affecting the maintenance of homeostasis of the central nervous system by the neuronal cells and fulfilling its neuroprotective effects（Fig. 7…

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Ribeiro, M.C. ...,Vitamin D supplementation rescues aberrant NF-κB pathway activation and partially ameliorates rett syndrome phenotypes in Mecp2 mutant mice
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Rocha, S.
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Sadeghian, N. ...,Calcitriol protects the Blood-Brain Barrier integrity against ischemic stroke and reduces vasogenic brain edema via antioxidant and antiapoptotic actions in rats
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Şahin, S. ...,Vitamin D protects against hippocampal apoptosis related with seizures induced by kainic acid and pentylenetetrazol in rats
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Sanchez, B. ...,1,25-Dihydroxyvitamin D3 administration to 6-hydroxydopamine-lesioned rats increases glial cell line-derived neurotrophic factor and partially restores tyrosine hydroxylase expression in substantia nigra and striatum
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12+ VitaminDWiki pages have NERV OR NEURO in the title

The list is automatically updated

Items found: 12

VitaminDWiki – Cognitive category contains:

Very brief summary of Cognitive decline
Treatment : Vitamin D intervention slows or stops progression
Prevention : Many observational studies - perhaps Vitamin D prevents
Omega-3 both prevents and treats cognition
Wonder the benefits if both Vitamin D AND Omega-3 were to be used
Dementia page - 50 items

389 items in Cognition category

see also Overview Alzheimer's-Cognition and Vitamin D
Overview Parkinson's and Vitamin D

Studies in both categories of Cognition and:
Cardiovascular (7 studies), Genetics (9 studies), Vitamin D Receptor (16 studies), Omega-3 (52 studies), Intervention (20 studies), Meta-analyses (22 studies), Depression (24 studies), Parkinson's (24 studies)
Click here for details

Poor cognition 26 percent more likely if low Vitamin D (29 studies) – meta-analysis July 2017
Every schizophrenia measure was improved when vitamin D levels were normalized – June 2021
Cognitive Impairment and Dementia often associated with low Vitamin D – April 2020
IQ levels around the world are falling (perhaps lower Vitamin D, Iodine, or Omega-3)
Search VitaminDWiki for "WHITE MATTER" 325 items as of March 2023

Types of evidence that Vitamin D helps brain problems - 2014
https://vitamindwiki.com/tiki-index.php?page_id=8392

Multiple Sclerosis 32 percent less likely among those with more than 32 ng of vitamin D – Dec 2019 contains

UV and Sunshine reduces MS risk

Other things also help

High Dose Vitamin D and cofactors

Number of MS studies which are also in other categories

  • 22 studies in Genetics - genes can restrict Vitamin D getting to the blood and to the cells
  • 14 studies in Vitamin D Receptor - gene which restricts D from getting to the cells
  • 7 studies in Vitamin D Binding Protein - gene which restricts D from getting to the cells
  • 21 studies in Ultraviolet light - may be even better than Vitamin D in preventing and treating MS
  • 9 studies in Omega-3 - which helps Vitamin D prevent and treat MS

VitaminDWiki – Autism category contains:

Autism category has 162 items

 - see also Overview Autism and vitamin D,  Autoimmune ,   Cognitive,    ADHD
Interesting Autistic studies
Autism associated with low Vitamin D

Autism treated by Vitamin D

Autism reduced by vitamins before and during pregnancy

Autism and Vitamin D Receptor (not enough Vit D gets to the cells)
This list is automatically updated

Autism - other risk factors

6 Autism and Virus/Vaccines

Dr. Cannell on Autism and Vitamin D in VitaminDWiki

7 studies: Autism reduced by Omega-3

VitaminDWiki – Overview Alzheimer's-Cognition and Vitamin D contains:

VitaminDWiki – Depression contains

Some recent publications

VitaminDWiki – Stroke category contains

131 items in stroke category - see also Overview Stroke and vitamin D,
Overview Hypertension and Vitamin D  Overview Cardiovascular and vitamin D

Stroke more likely if low Vitamin D

Post-Stroke worse if low Vitamin D

Post-Stroke better if add Vitamin D

Post-Stroke better if Vitamin D actually gets to cells

11 studies in both categories of Depression and Stroke

This list is automatically updated

VitaminDWiki – Overview Epileptic children and Vitamin D category contains

Fact: Anti-epilepsy drugs lower vitamin D levels
Fact: Epilepsy 5X more likely if preterm birth (low vitamin D)
Fact: Preterm greatly decreased if add vitamin D and/or Omega-3
Fact: Vitamin D supplementation increases Vitamin D levels
Recommendation: Epileptics should take vitamin D to:
    Reduce the number of seizures (restore vitamin D then take a maintenance dose of at least 5,000 IU daily)
   Avoid having health problems associated with low vitamin D, such as low bone density
1 study: Epileptics have low vitamin D levels before starting treatment
Epilepsy = 4,000 years of ignorance, superstition and stigma
   followed by 100 years of knowledge, superstition and stigma.




Nerve cells and Vitamin D – many studies        
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Depression 262 Autism 152 Cognitive 387 Stroke 129 Spinal Cord 20 Epilepsy 16
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