Evidence of functional vitamin D receptors in rat hippocampus

Langub, M. Chris; Herman, James P.; Malluche, Hartmut H.; Koszewski, Nicholas J.

doi:10.1016/s0306-4522(01)00049-5

Cited by 143 publications

(106 citation statements)

References 47 publications

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“…Thus, we suggest that the polymorphism in the ligand binding site of the VDR gene increases the risk for AD development. Our findings are also in correlation with studies that show the wider biological role for vitamin D in brain (Chatterjee 2001;Langbug et al 2001;Garcion et al 2002;Eyles et al 2003). Those studies demonstrated that vitamin D can act on nervous system by modulating the expression of neurotrophins (Neveu et al 1994a, b;Garcion et al 2002).…”

Section: Discussionsupporting

confidence: 91%

Association between Vitamin D Receptor Gene Polymorphism and Alzheimer's Disease

Gezen-Ak

Dursun

Ertan

et al. 2007

Tohoku J. Exp. Med.

138

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Vitamin D 3 is known to be involved in neuroprotection and exert its neuroprotective effects by modulating neuronal calcium homeostasis and production of neurotrophins. The single nucleotide polymorphisms (SNP) in vitamin D receptor (VDR) gene which can influence the affinity of vitamin D 3 to its receptor may be related to neurodegenerative diseases and neuronal damage by altering the vitamin D-mediated pathways. In this study, our aim was to determine whether there is an association between VDR gene and lateonset Alzheimer's disease (AD) in order to see if vitamin D contributes to AD or not. One hundred and four cases of dementia of Alzheimer type and 109 age-matched controls were genotyped according to ApaI (a: + restriction site and A: no restriction site) and TaqI (t: + restriction site and T: no restriction site) sites in intron 8 and exon 9 of the ligand-binding site of VDR gene. When the controls and patients were compared for their ApaI genotypes, the frequency of the patients with Aa genotype was significantly higher than the frequency of the healthy individuals with the same genotype ( p = 0.008, χ 2 = 9.577, OR = 2.30). Thus, the "Aa" genotype may increase the risk of developing AD 2.3 times when compared with the "AA" genotype. On the other hand, the "AT" haplotype was significantly higher in controls ( p = 0.006) indicating a protective role of the "AT" haplotype in AD. Consequently, this study provides evidence for a possible link between AD and vitamin D. vitamin D; VDR; Alzheimer's disease; SNP; haplotype © 2007 Tohoku University Medical PressThe most common form of degenerative dementia is Alzheimer's disease (AD) constituting approximately 60-70% of cases (Emilien et al. 2004). It is a chronic, degenerative, dementing illness with typically insidious onset (Rocca et al. 1991). The key aims in therapeutic strategies of AD are to decrease the neuronal damage, provide maintenance or regeneration of neu r o n s

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Section: Discussionsupporting

confidence: 91%

Association between Vitamin D Receptor Gene Polymorphism and Alzheimer's Disease

Gezen-Ak

Dursun

Ertan

et al. 2007

Tohoku J. Exp. Med.

138

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“…Several proteins (VDR, synaptojanin 1, and synaptotagmin 2) were selected for analysis by IHC. Consistent with prior studies, the presence of VDR was confirmed in hippocampal neurons (18,19). No difference in VDR staining was detected between groups (Fig.…”

Section: Significancesupporting

confidence: 91%

“…Because the brain expresses vitamin D receptors (VDRs) and can synthesize the active form of the hormone, the possible cognitive enhancing effects of vitamin D may reflect a primary action in the brain rather than a result of secondary systemic effects (18)(19)(20)(21)(22). Indeed, we and others have shown that vitamin D, as well as the biologically active form of the hormone, 1,25-dihydroxyvitamin D, has direct neuroprotective actions and can reduce some biomarkers of brain aging (20,(23)(24)(25)(26)(27)(28).…”

mentioning

confidence: 99%

Vitamin D prevents cognitive decline and enhances hippocampal synaptic function in aging rats

Latimer¹,

Brewer²,

Searcy³

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

186

103

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Vitamin D is an important calcium-regulating hormone with diverse functions in numerous tissues, including the brain. Increasing evidence suggests that vitamin D may play a role in maintaining cognitive function and that vitamin D deficiency may accelerate agerelated cognitive decline. Using aging rodents, we attempted to model the range of human serum vitamin D levels, from deficient to sufficient, to test whether vitamin D could preserve or improve cognitive function with aging. For 5-6 mo, middle-aged F344 rats were fed diets containing low, medium (typical amount), or high (100, 1,000, or 10,000 international units/kg diet, respectively) vitamin D3, and hippocampal-dependent learning and memory were then tested in the Morris water maze. Rats on high vitamin D achieved the highest blood levels (in the sufficient range) and significantly outperformed low and medium groups on maze reversal, a particularly challenging task that detects more subtle changes in memory. In addition to calcium-related processes, hippocampal gene expression microarrays identified pathways pertaining to synaptic transmission, cell communication, and G protein function as being up-regulated with high vitamin D. Basal synaptic transmission also was enhanced, corroborating observed effects on gene expression and learning and memory. Our studies demonstrate a causal relationship between vitamin D status and cognitive function, and they suggest that vitamin D-mediated changes in hippocampal gene expression may improve the likelihood of successful brain aging.V itamin D, a secosteroid hormone known for its role in bone and calcium homeostasis, is now well recognized for its many diverse functions and actions on a variety of tissues and cell types (1, 2). Vitamin D typically refers to the precursor forms of the hormone obtained through the skin's exposure to sunlight [vitamin D3 (VitD3)] or from dietary sources (VitD3 or VitD2). A metabolite of vitamin D, 25-hydroxyvitamin D (25OHD), is a serum biomarker of vitamin D status or repletion. In recent years, there is particular concern that large segments of the population may have low levels of 25OHD, and therefore are vitamin D-deficient (3). Due to factors such as reduced intake, absorption, and decreased exposure to sunlight, aging adults (≥50 y of age) are especially susceptible (3-6). Notably, this predisposition for lower 25OHD levels in the elderly has been linked to higher risk for numerous age-related disorders, including cancer and metabolic and vascular diseases (7-10).Inadequate vitamin D status also correlates with a greater risk for cognitive decline in the elderly (4,(11)(12)(13)(14)(15), suggesting that optimal levels may promote healthy brain aging (16,17). Because the brain expresses vitamin D receptors (VDRs) and can synthesize the active form of the hormone, the possible cognitive enhancing effects of vitamin D may reflect a primary action in the brain rather than a result of secondary systemic effects (18)(19)(20)(21)(22). Indeed, we and others have shown that vitamin D, as ...

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“…Animal studies revealed the presence of VDR in the neuroepithelium during early neurogenesis, and in later stages, in an area involved in the maintenance of neural stem cells, the subventricular zone (Veenstra 1998). More recent animal data confirm the expression of VDR in specific brain regions, including but not limited to, the temporal lobe, cingulate cortices, thalamus, cerebellum, amygdala and hippocampal regions (Clemens, Garrett et al 1988;Stumpf, Clark et al 1988;Prufer, Veenstra et al 1999;Langub, Herman et al 2001;Garcion, Wion-Barbot et al 2002;Eyles, Brown et al 2003;McGrath, Feron et al 2004). …”

Section: Vitamin D and The Brain: Mechanisms Of Actionmentioning

confidence: 82%