Vitamin D shows associations between low levels of vitamin D, or hypovitaminosis D, and neuropsychiatric disorders, including Alzheimer's disease, autism, epilepsy, multiple sclerosis, Parkinson's disease, and schizophrenia.
Physiology Vitamin D (the inactive version) is mainly from two forms: vitamin D3 and vitamin D2. Vitamin D3, or cholecalciferol, is formed in the skin after exposure to sunlight or ultra violet radiation or from D3 supplements or fortified food sources. Vitamin D2, or ergocalciferol, is obtained from D2 supplements or fortified food sources. These two forms of vitamin D are metabolized in the liver and stored as 25-hydroxyvitamin D. Before biological use, the storage form must be converted into an active form. One common active form is 1,25-dihydroxyvitamin D. The term vitamin D in this article means cholecalciferol, ergocalciferol, 25-hydroxyvitamin D, and the active forms. The role of vitamin D is best characterized as enabling calcium absorption and regulating calcium homeostasis. Vitamin D also play a role in phosphate absorption.
Hypovitaminosis D Hypovitaminosis D is any deficiency of vitamin D. A vitamin D blood-concentration standard for diagnosing hypovitaminosis D does not exist. In the past, hypovitaminosis D was defined by blood concentrations lower than 20 ng/mL. However, in more recent literature many researchers have considered 30 ng/mL to be an insufficient concentration of vitamin D. Subnormal levels of vitamin D are usually caused by poor nutrition or a lack of sun exposure. Risk factors for hypovitaminosis D include premature birth, darker skin pigmentation, obesity, malabsorption, and older age.
Vitamin D and the central nervous system
Location in the central nervous system The brain requires the use of many neurosteroids to develop and function properly. These molecules are often identified as one of many common substances including thyroid hormones, glucocorticoids, and sex hormones. However in recent studies, throughout the brain and spinal fluid, vitamin D has begun to surface as one of these neurosteroids.
Metabolites: Several vitamin D metabolites are found in cerebral spinal fluid and have the ability to cross the blood brain barrier. This is similar to many of the previously known neurosteroids. These vitamin D metabolites include 25-hydroxyvitamin D3, 1,25-dihydroxyvitamin D3, and 24,25-dihydroxyvitamin D3. Derivatives of these metabolites are highly expressed in the substantia nigra and the hypothalamus. These two brain structures are responsible for motor functions and linking the nervous system to the endocrine system, respectively. The expression of these metabolite derivatives in these areas suggests that these structures have the ability to synthesize these products from vitamin D.
Receptors: In addition to vitamin D metabolites, vitamin D receptor (VDR) proteins are also found in the brain; more specifically, they are found in the cerebellum, thalamus, hypothalamus, basal ganglia, and hippocampus. The highest density of VDR is in substantia nigra, one of the primary areas of dopamine production. Another significant portion of the receptors is located in the hypothalamus (supra optic and paraventricular nuclei) and external granule cell layer of the prefrontal cortex. VDR are also found in the hippocampus (CA1 and CA2) areas, in slightly lower densities.
Function in the central nervous system The presence of vitamin D, its activating enzyme, and VDR in the brain leads researchers to question what role vitamin D plays in the brain. Research suggests that vitamin D may function as a modulator in brain development and as a neuroprotectant. In recent studies, vitamin D has exhibited an association with the regulation of nerve growth factor (NGF) synthesis. NGF is responsible for the growth and survival of neurons. This relationship has also been studied in embryonic and neonatal rats. Developmental vitamin D deficient (DVD) rats have decreased levels of neurotrophic factors, increased mitosis, and decreased apoptosis. These findings suggest that vitamin D potentially affects the development of neurons as well as their maintenance and survival. Current research is underway investigating whether vitamin D is a factor contributing to normal brain functioning.
Vitamin D and neurological disorders Hypovitaminosis D is associated with several neuropsychiatric disorders including dementia, Parkinson's disease, multiple sclerosis, epilepsy, and schizophrenia. There are several proposed mechanisms by which hypovitaminosis D may impact these disorders. One of these mechanisms is through neuronal apoptosis. Neuronal apoptosis is the programmed death of the neurons. Hypovitaminosis D causes this specific apoptosis by decreasing the expression of cytochrome C and decreasing the cell cycle of neurons. Cytochrome C is a protein that promotes the activation of pro-apoptotic factors. A second mechanism is through the association of neurotrophic factors like nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF). These neurotrophic factors are proteins that are involved in the growth and survival of developing neurons and they are involved in the maintenance of mature neurons.
Dementia: Alzheimer's disease "Dementia" is a term referring to neurodegenerative disorders characterized by a loss of memory and such brain functions as executive functioning. Included under this umbrella term is Alzheimer's disease. Alzheimer's disease is characterized by the loss of cortical functions like language and motor skills. Patients with Alzheimer's disease exhibit an extreme shrinkage of the cerebral cortex and hippocampus with an enlargement of the ventricles. In several recent studies, higher vitamin D levels have been associated with lower risks of developing Alzheimer's disease. Alzheimer's disease is associated with a decrease in vitamin D receptors in the Cornu Ammonius areas (CA 1& 2) of the hippocampus. The hippocampus is a portion of the limbic system responsible for memory and spatial navigation. Additionally, certain VDR haplotypes were detected with increased frequency in patients with Alzheimer's disease while other VDR haplotypes were detected with decreased frequency, suggesting that specific haplotypes may increase or decrease risk of developing Alzheimer's. It is hypothesized that this lack of VDRs in the hippocampus prevents the proper functioning (ie. memory) of this structure.
… excerpt ends here. Continue reading the full article.
