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J P Grande

Publications and source records attributed to J P Grande.

At least 19 recordsLinked to original sources
PubMed2002

Ontogeny of Phex/PHEX protein expression in mouse embryo and subcellular localization in osteoblasts.

PHEX, a phosphate-regulating gene with homologies to endopeptidases on the X chromosome, is mutated in X-linked hypophosphatemia (XLH) in humans and mice (Hyp). Although recent observations indicate that Phex protein is expressed primarily in bone and may play an important role in osteoblast function and bone mineralization, the pattern of the Phex protein expression in the developing skeleton and its subcellular localization in osteoblasts remain unknown. We examined the ontogeny of the Phex protein in the developing mouse embryo and its subcellular localization in osteoblasts using a specific antibody to the protein. Immunohistochemical staining of mouse embryos revealed expression of Phex in osteogenic precursors in developing vertebral bodies and developing long bones on day 16 postcoitum (pc) and thereafter. Calvaria from day 18 pc mice showed Phex epitopes in osteoblasts. No Phex immunoreactivity was detected in lung, heart, hepatocytes, kidney, intestine, skeletal muscle, or adipose tissue of mouse embryos. Interestingly, embryonic mouse skin showed moderate amounts of Phex immunostaining. In postnatal mice, Phex expression was observed in osteoblasts and osteocytes. Moderate expression of Phex was seen in odontoblasts and slight immunoreactivity was observed in ameloblasts. Confocal microscopy revealed the presence of immunoreactive PHEX protein in the Golgi apparatus and endoplasmic reticulum of osteoblasts from normal mice and in osteoblasts from Hyp mice transduced with a human PHEX viral expression vector. PHEX protein was not detected in untransduced Hyp osteoblasts. These data indicate that Phex protein is expressed in osteoblasts and osteocytes during the embryonic and postnatal periods and that within bone, Phex may be a unique marker for cells of the osteoblast/osteocyte lineage.

Amino Acid Sequence↗
PubMed2001

Load versus humoral activation in the genesis of early hypertensive heart disease.

BACKGROUND: The role of load versus angiotensin II (Ang II) and endothelin-1 (ET) in the pathogenesis of hypertensive heart disease is controversial. We sought to determine whether alterations in cardiac structure and function due to hypertension (HTN) were dependent on Ang II or ET activation. Methods and Results-- Bilateral renal wrapping to produce HTN (n=12) or sham surgery (n=6) was performed in adult dogs. Weekly blood pressure, plasma renin activity, Ang II, ET, and catecholamines were measured. Systolic (end-systolic elastance, Ees) and diastolic (tau) function were assessed in sham and HTN dogs at 5 (HTN-5wk) or 12 (HTN-12wk) weeks. Ang II and ET were assayed in the left ventricle (LV) and kidney. Mean arterial pressure was higher in renal wrap dogs at week 1 (*P<0.05 versus controls: 139+/-4* versus 123+/-4 mm Hg), week 5 (174+/-7* versus 124+/-4 mm Hg), and week 12 (181+/-12* versus 124+/-4 mm Hg). LV mass index was increased in HTN-5wk (22%*) and HTN-12wk (39%*). LV fibrosis was increased in HTN-12wk. Ees was preserved in HTN-5wk and HTN-12wk. tau was increased in HTN-5wk (50+/-3* ms) and HTN-12wk (62+/-10* ms) dogs compared with sham (41+/-2 ms). Plasma Ang II, ET, catecholamines, and plasma renin activity were unchanged during the progressive HTN. Ang II and ET in LV and kidney were not different from controls. CONCLUSIONS: Systemic HTN induces LV hypertrophy, myocardial fibrosis, and isolated diastolic dysfunction in the absence of local or systemic activation of Ang II or ET. These findings suggest that load is the prevailing stimulus for the structural and functional changes associated with early hypertensive heart disease.

Angiotensin II↗
PubMed2001

Nicotinic acid-adenine dinucleotide phosphate (NAADP) elicits specific microsomal Ca2+ release from mammalian cells.

Nicotinic acid-adenine dinucleotide phosphate (NAADP), a molecule derived from beta-NADP, has been shown to promote intracellular calcium release in sea urchin eggs. However, there is little information regarding the role of NAADP in the regulation of intracellular calcium fluxes in mammalian cells. We found recently that several mammalian tissues have a high capacity for NAADP synthesis, as assessed by sea urchin egg bioassay. To determine the functional significance of NAADP production by mammalian tissues, we sought to determine whether NAADP is capable of inducing calcium release from microsomes prepared from cultured cells. We found that NAADP, but not beta-NADP, activates a specific microsomal calcium release system in mesangial cells isolated from rat kidney; NAADP was without effect in renal tubular epithelial cells. NAADP-induced calcium release is not affected by inhibitors of the inositol 1,4,5-trisphosphate or ryanodine channels. However, NAADP-elicited calcium release was inhibited by L-type calcium channel blockers and by alkaline phosphatase treatment of NAADP. NAADP also promotes specific microsomal calcium release in rat vascular smooth muscle cells, cardiac myocytes, fibroblasts and a human leukaemia cell line, indicating that the capacity for NAADP-induced calcium release is widespread in mammalian cells. We propose that NAADP may be an important regulator of intracellular calcium in many mammalian tissues.

Adenosine Diphosphate Ribose↗
PubMed2001

Expression of an immediate early gene, IEX-1, in human tissues.

IEX-1 is an immediate early gene that is induced by ionizing radiation, ultraviolet radiation, and a variety of growth factors. It plays an important role in the regulation of cellular growth. Earlier, we performed studies on the distribution of IEX-1 messenger RNA in different tissues and on the subcellular localization of IEX-1 protein. No reports, however, have appeared concerning the distribution of IEX-1 protein in a variety of human tissues. We raised a polyclonal antibody against a synthetic IEX-1 peptide (amino acids 51-75) and used the antibody to study the distribution of the protein in human tissues. We demonstrate that IEX-1 is strongly expressed in epithelia of the skin, trachea, gastrointestinal, and genitourinary systems, as well as in the pancreas and breast. Endothelial cells within the vasculature of most tissue/organs also strongly express IEX-1. Liver, lung, lymph nodes, and placenta stain weakly. No IEX-1 epitopes were detected in the thymus, testes, ovary, myocardium, skeletal muscle, or spleen. We conclude that IEX-1 is widely expressed in epithelial and endocrine tissues, as well as in vascular endothelium.

Amino Acid Sequence↗
PubMed2001

Oxidative stress and induction of heme oxygenase-1 in the kidney in sickle cell disease.

Chronic nephropathy is a recognized complication of sickle cell disease. Using a transgenic sickle mouse, we examined whether oxidative stress occurs in the sickle kidney, the origins and functional significance of such oxidant stress, and the expression of the oxidant-inducible, potentially protective gene, heme oxygenase-1 (HO-1); we also examined the expression of HO-1 in the kidney and in circulating endothelial cells in sickle patients. We demonstrate that this transgenic sickle mouse exhibits renal enlargement, medullary congestion, and a reduced plasma creatinine concentration. Oxidative stress is present in the kidney as indicated by increased amounts of lipid peroxidation; heme content is markedly increased in the kidney. Exacerbation of oxidative stress by inhibiting glutathione synthesis with buthionine-sulfoximine dramatically increased red blood cell sickling in the sickle kidney: in buthionine-sulfoximine-treated sickle mice, red blood cell sickling extended from the medulla into the cortical capillaries and glomeruli. HO activity is increased in the sickle mouse kidney, and is due to induction of HO-1. In the human sickle kidney, HO-1 is induced in renal tubules, interstitial cells, and in the vasculature. Expression of HO-1 is increased in circulating endothelial cells in patients with sickle cell disease. These results provide the novel demonstration that oxidative stress occurs in the sickle kidney, and that acute exacerbation of oxidative stress in the sickle mouse precipitates acute vaso-occlusive disease. Additionally, the oxidant-inducible, heme-degrading enzyme, HO-1, is induced regionally in the murine and human sickle kidney, and systemically, in circulating endothelial cells in sickle patients.

Anemia, Sickle Cell↗
PubMed2001

Heme protein-induced chronic renal inflammation: suppressive effect of induced heme oxygenase-1.

BACKGROUND: Heme oxygenase (HO) is the rate-limiting enzyme in the degradation of heme; its inducible isozyme, HO-1, protects against acute heme protein-induced nephrotoxicity and other forms of acute tissue injury. This study examines the induction of HO-1 in the kidney chronically inflamed by heme proteins and the functional significance of such an induction of HO-1. METHODS: Studies were undertaken in a patient with chronic tubulointerstitial disease in the setting of paroxysmal nocturnal hemoglobinuria (PNH), in a rat model of chronic tubulointerstitial nephropathy caused by repetitive exposure to heme proteins, and in genetically engineered mice deficient in HO-1 (HO-1 -/-) in which hemoglobin was repetitively administered. RESULTS: The kidney in PNH evinces robust induction of HO-1 in renal tubules in the setting of chronic inflammation. The heme protein-enriched urine from this patient, but not urine from a healthy control subject, induced expression of HO-1 in renal tubular epithelial cells (LLC-PK1 cells). A similar induction of HO-1 and related findings are recapitulated in a rat model of chronic inflammation induced by repetitive exposure to heme proteins. Additionally, in the rat, the administration of heme proteins induces monocyte chemoattractant protein (MCP-1). The functional significance of HO-1 so induced was uncovered in the HO-1 knockout mouse: Repeated administration of hemoglobin to HO-1 +/+ and HO-1 -/- mice led to intense interstitial cellular inflammation in HO-1 -/- mice accompanied by striking up-regulation of MCP-1 and activation of one of its stimulators, nuclear factor-kappaB (NF-kappaB). These findings were not observed in similarly treated HO-1 +/+ mice or in vehicle-treated HO-1 -/- and HO-1 +/+ mice. CONCLUSION: We conclude that up-regulation of HO-1 occurs in the kidney in humans and rats repetitively exposed to heme proteins. Such up-regulation represents an anti-inflammatory response since the genetic deficiency of HO-1 markedly increases activation of NF-kappaB, MCP-1 expression, and tubulointerstitial cellular inflammation.

Adult↗
PubMed2001

Acute cholestatic liver disease protects against glycerol-induced acute renal failure in the rat.

BACKGROUND: It is widely held that liver disease predisposes toward acute tubular necrosis. The present study examines the effect of acute cholestatic liver disease on the susceptibility to glycerol-induced acute tubular necrosis in the rat. METHODS: Acute cholestatic liver disease was induced by ligation of the common bile duct, while the intramuscular injection of hypertonic glycerol was used to induce acute tubular necrosis. Renal injury was assessed by plasma creatinine concentration and renal histology. An in vitro model of heme protein-induced renal injury (hemoglobin in conjunction with glutathione depletion) was employed to assess the cytoprotective effects of bilirubin. RESULTS: Ligation of the common bile duct markedly reduced acute renal injury that occurs in the glycerol model (7.5 mL/kg body weight), as evidenced by a lower plasma creatinine concentration and less severe renal histologic injury. At a higher dose of glycerol (10 mL/kg body weight), ligation of the common bile duct again reduced renal injury and cumulative mortality that occurs five days after the induction of this model of acute renal failure. These protective effects of ligation of the common bile duct could not be ascribed to less severe muscle injury or red cell damage. Ligation of the common bile duct induced heme oxygenase-1 in the kidney and markedly so in the liver. Inhibition of heme oxygenase significantly attenuated, but did not prevent, the protective effects conferred by ligation of the common bile duct. Bilirubin, in low micromolar concentrations, was cytoprotective against heme protein-induced cell injury in vitro. CONCLUSIONS: Ligation of the common bile duct confers resistance to glycerol-induced acute tubular necrosis in the rat, actions that arise, in part, from the induction of heme oxygenase-1 in the kidney and liver. Bilirubin, in micromolar concentrations, protects against heme protein-induced renal injury. Our studies uncover a novel form of acquired resistance to renal injury, occurring, unexpectedly, in the setting of acute cholestatic liver disease. We speculate that such potentially cytoprotective alterations may safeguard the kidney against irreversible functional and structural injury in the hepatorenal syndrome.

Acute Kidney Injury↗
PubMed2001

cADP-ribose/ryanodine channel/Ca2+-release signal transduction pathway in mesangial cells.

Signaling via release of Ca2+ from intracellular stores is mediated by several systems, including the inositol 1,4,5-trisphosphate (IP3) and cADP-ribose (cADPR) pathway. We recently discovered a high capacity for cADPR synthesis in rat glomeruli and cultured mesangial cells (MC). We sought to determine whether 1) cADPR synthesis in MC is regulated by cytokines and hormones, 2) ryanodine receptors (RyRs) are expressed in MC, and 3) Ca2+ is released through RyRs in response to cADPR. We found that ADP-ribosyl cyclase, a CD38-like enzyme that catalyzes cADPR synthesis, is upregulated in MC by tumor necrosis factor-alpha, interleukin-1beta, and all-trans retinoic acid (atRA). [3H]ryanodine binds to microsomal fractions from MC with high affinity in a Ca2+-dependent manner; binding is enhanced by specific RyR agonists and blocked by ruthenium red and cADPR. Western blot analysis confirmed the presence of RyR in MC. Release of 45Ca2+ from MC microsomes was stimulated by cADPR; release was blocked by ruthenium red and 8-bromo-cADPR. ADPR (non-cyclic) was without effect. In MC, TNF-alpha and atRA amplified the increment of cytoplasmic Ca2+ elicited by vasopressin. We conclude that MC possess elements of a novel ADP-ribosyl cyclase-->cADPR-->RyR-->Ca2+-release signaling pathway subject to regulation by proinflammatory cytokines and steroid superfamily hormones.

ADP-ribosyl Cyclase↗
PubMed2001

Role of dietary fish oil supplementation in IgA nephropathy. Mechanistic implications.

IgA nephropathy (IgAN) is now recognized as the most common primary glomerulonephritis worldwide. Although the clinical course is variable, many patients develop slowly progressive renal disease, culminating in end-stage renal disease 10-20 years after diagnosis. Some recent randomized clinical trials have suggested that dietary fish oil supplementation may be a relatively safe long-term therapeutic option for preventing the development of progressive renal disease in patients with IgAN. However, other studies have failed to demonstrate a protective effect of dietary fish oil supplementation in treatment of IgAN. Although in vitro studies have provided a theoretical basis for the use of dietary fish oil supplementation, potential mechanisms underlying the protective effect of fish oil have not been well defined. In this overview, recent clinical and experimental data providing a basis for the use of dietary fish oil supplementation in treatment of IgAN and other progressive renal diseases are reviewed.

Animals↗
PubMed2000

The indispensability of heme oxygenase-1 in protecting against acute heme protein-induced toxicity in vivo.

Heme oxygenase (HO) is the rate limiting enzyme in the degradation of heme, and its isozyme, HO-1, may protect against tissue injury. One posited mechanism is the degradation of heme released from destabilized heme proteins. We demonstrate that HO-1 is a critical protectant against acute heme protein-induced toxicity in vivo. In the glycerol model of heme protein toxicity-one characterized by myolysis, hemolysis, and kidney damage-HO-1 is rapidly induced in the kidney of HO-1 +/+ mice as the latter sustain mild, reversible renal insufficiency without mortality. In stark contrast, after this insult, HO-1 -/- mice exhibit fulminant, irreversible renal failure and 100% mortality; HO-1 -/- mice do not express HO-1, and evince an eightfold increment in kidney heme content as compared to HO-1 +/+ mice. We also demonstrate directly the critical dependency on HO-1 in protecting against a specific heme protein, namely, hemoglobin: doses of hemoglobin which exert no nephrotoxicity or mortality in HO-1 +/+ mice, however, precipitate rapidly developing, acute renal failure and marked mortality in HO-1 -/- mice. We conclude that the induction of HO-1 is an indispensable response in protecting against acute heme protein toxicity in vivo.

Acute Kidney Injury↗
PubMed2000

Renal response to repetitive exposure to heme proteins: chronic injury induced by an acute insult.

BACKGROUND: Renal diseases are conventionally classified into acute and chronic disorders. We questioned whether acute, reversible, renal insults may be induced to incite a chronic scarring process, employing as an acute insult the glycerol model of heme protein-induced renal injury. METHODS: Rats were subjected to weekly injections of hypertonic glycerol for up to six months. Renal function was serially determined, and the effect of such insults on renal histology and renal expression of collagen and fibrogenic cytokines was assessed. RESULTS: After the first injection of glycerol, which, expectedly, induced a prompt fall in the glomerular filtration rate (GFR), subsequent injections encountered a remarkable renal resistance in that the fall in GFR was markedly blunted. This resistance to acute decline in renal function in rats subjected to repetitive injections of glycerol was accompanied by less necrosis and apoptosis of renal tubular epithelial cells after such injections. The attenuation in the fall in GFR in response to repetitive exposure to glycerol-induced heme protein injury was maintained for up to six months. A progressive decline in GFR appeared after three months and was accompanied by histologic tubulointerstitial injury, the latter assessed at six months. These kidneys demonstrated up-regulation of collagen I, III, and IV in conjunction with increased expression of the oxidant-inducible, chemotactic cytokine, monocyte chemoattractant protein-1 (MCP-1), and the oxidant-inducible, fibrogenic cytokine, transforming growth factor-beta1 (TGF-beta1). The exposure of the kidney to a single injection of hypertonic glycerol increased the expression of both cytokines some three to five days following this exposure, while the exposure of NRK 49F cells in culture to an iron-dependent model of oxidative stress also increased expression of TGF-beta1 and collagen mRNAs. CONCLUSIONS: We conclude that this nephrotoxic insult, repetitively administered, encounters a resistance in the kidney such that the expected fall in GFR does not occur. However, with time, such resistance is accompanied by a decrease in GFR, the latter associated with chronic tubulointerstitial disease. Thus, a long-term cost is exacted, either along with, or as a consequence of, such resistance. We suggest that chronic up-regulation of such oxidant-inducible genes such as TGF-beta1 and MCP-1 contributes to tubulointerstitial disease, and iron-mediated oxidative stress may directly induce TGF-beta1.

Acute Disease↗
PubMed2000

Suppressive effects of fish oil on mesangial cell proliferation in vitro and in vivo.

BACKGROUND: Mesangial cell proliferation is a characteristic feature of IgA nephropathy and many other forms of glomerulonephritis. Recent clinical studies have shown that dietary fish oil supplementation retards renal disease progression in patients with IgA nephropathy. The mechanism by which this effect occurs is unknown. METHODS: The anti-Thy 1.1 (ATS) model of mesangial proliferative glomerulonephritis was employed to test the hypothesis that dietary fish oil supplementation reduces mesangial cell proliferation following acute injury. Subcultured rat mesangial cells were used to determine the in vitro effects of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), the primary components of fish oil, on proliferation. RESULTS: Following antithymocyte serum (ATS) administration, proteinuria was significantly decreased in animals treated with fish oil compared with sesame oil-treated controls. In ATS rats given fish oil, there was less mesangial cell and matrix expansion, mesangiolysis, or basement membrane disruption (delta% = -40%). ATS rats receiving fish oil had less glomerular cell proliferation (PCNA-delta% = -50%) and a reduction of alpha-smooth muscle actin expression (delta% = -27%) by mesangial cells. In subcultured rat mesangial cells, DHA, but not EPA, significantly inhibited proliferation. CONCLUSIONS: Fish oil inhibits mesangial cell activation and proliferation in ATS glomerulonephritis, reduces proteinuria, and decreases histologic evidence of glomerular damage. In vitro, the antiproliferative effects of fish oil are more likely related to the action of DHA. We suggest that orally administered fish oil, or purified DHA, may have a suppressive effect in acute phases or relapses of glomerulopathies by inhibiting activation and proliferation of mesangial cells.

Animals↗
PubMed2000

Pancreas transplantation for the prevention of diabetic nephropathy.

Diabetic nephropathy is the leading cause of kidney failure in the United States. Poor glycemic control, hypertension, and smoking have been implicated as risk factors for the development and progression of diabetic nephropathy in patients with type 1 diabetes mellitus. Improved medical therapy including angiotensin-converting enzyme inhibitors and tight glycemic control with use of intensive insulin therapy have been shown to reduce the progression of diabetic nephropathy substantially based on albumin excretion rates. Despite these improvements in medical management, many patients still experience progression from early diabetic nephropathy to end-stage renal disease. Successful pancreas transplantation leads to normal glycemic control in patients with type 1 diabetes, but historically it has generally been limited to patients with both kidney failure and diabetes. In this review of the current treatment of diabetic nephropathy, we examine the potential role of preemptive pancreas transplantation in patients with diabetic nephropathy.

Albuminuria↗
PubMed1999

Noninvasive evaluation of a novel swine model of renal artery stenosis.

Intrarenal hemodynamics and excretory function distal to renal artery stenosis are difficult to quantify noninvasively. In this study, a swine model of chronic unilateral renal artery stenosis, achieved by implantation of an intravascular device that leads to a gradual and progressive luminal area narrowing, was developed and evaluated. Bilateral cortical and medullary volumes, blood flows, and segmental tubular dynamics were assessed in the intact kidneys of seven pigs using electron-beam computerized tomography before and 1 mo after implantation of the device. Within 1 mo, a 66% angiographic stenosis was significantly correlated with a 25% increase in BP. The volume and blood flow were markedly lower in the stenotic compared with the contralateral kidney and cortex, while the medulla exhibited minimal changes. In the stenotic kidney, intratubular contrast content has decreased in all nephron segments, especially in the distal tubule, where it correlated with an increase in serum creatinine and stenosis severity. In the contralateral kidney, dilution of proximal tubular fluid correlated with the increase in BP, likely due to pressure-natriuresis. In conclusion, the swine model closely resembles human renovascular hypertension. In the stenotic kidney, the hemodynamic impairment of the cortex is dissociated from the relatively preserved renal medulla, and the earliest effect on excretory function is observed in the distal nephron, where the fall in the amount of fluid reaching that segment is directly proportional to the renal arterial compromise. Electron-beam computerized tomography shows promise to noninvasively quantify, follow-up, and study changes in concurrent, in vivo intrarenal hemodynamics and segmental tubular function in renovascular hypertension.

Animals↗
PubMed1999

The long-term outcome of patients with IgA nephropathy treated with fish oil in a controlled trial. Mayo Nephrology Collaborative Group.

It was reported previously that dietary fish oil supplementation retarded the progression of renal disease in patients with IgA nephropathy in a multicenter, placebo-controlled, randomized, 2-yr clinical trial. The aim of this study was to determine the long-term influence of fish oil treatment on renal progression in observations on the study cohort of 106 patients extending beyond the 2-yr trial. Renal function was assessed by serial serum creatinine and 24-h urine protein measurements. Vital, end-stage renal disease (ESRD), and BP status and treatment beyond completion of the 2-yr trial were determined. As in the trial, the primary end point was an increase of 50% or more in the serum creatinine, and the secondary end point was ESRD. After a mean follow-up of 6.4 yr, 46 patients-17 in the fish oil group versus 29 in the placebo group-reached the primary end point (P = 0.002), and 27 patients-eight in the fish oil group versus 19 in the placebo group-developed ESRD (P = 0.009). At the end of the 2-yr trial, 75 patients (45 fish oil, 30 placebo) remained at risk for the primary end point. This is also when the double-blind part of the trial ended, allowing physicians to stop supplements, switch original placebo-assigned patients to fish oil, and continue fish oil in original fish oil-assigned patients. A significantly greater number of nonsupplemented placebo patients developed the primary end point (P = 0.02) and ESRD (P = 0.003) compared with long-term supplemented fish oil patients. Conversely, more fish oil-supplemented patients had stable renal function than nonsupplemented patients (P = 0.02). By intention, BP control, primarily treated with angiotensin-converting enzyme inhibition, was equal in the fish oil and placebo groups. Proteinuria was modestly reduced in both groups. It is concluded that early and prolonged treatment with fish oil slows renal progression for high-risk patients with IgA nephropathy.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1998

1,25-Dihydroxyvitamin D3 receptors in the central nervous system of the rat embryo.

We have mapped areas within the central nervous system (CNS) of the developing fetal rat which immunostain for the 1,25-dihydroxyvitamin D3 receptor (VDR). The VDR was detected from days 12 to 21 of gestation throughout the CNS; immunostaining was particularly intense in the neuroepithelium and within the differentiating fields of various areas of the brain. Cells within the spinal cord, dorsal root, and other ganglia exhibited positive staining for the VDR. The intensity of staining for the VDR diminished or disappeared in the neuroepithelium throughout the CNS during the later days of development, while in the differentiating fields single VDR immunoreactive cells were observed. The presence of the VDR in the CNS was confirmed by in situ hybridization and RNA-based polymerase chain reaction methods with di-deoxy sequencing of the resultant DNA product. These results support the hypothesis that 1, 25-dihydroxyvitamin D3, through interactions with the VDR, may play a role in the development of the CNS.

Animals↗