Parkinson's Disease Correlation
Correlation Between Vitamin D Deficiency and Parkinson’s Disease
Trisakti University of Medicine
I Made Setiadji
030.09.114
Jakarta, June 14th 2012
Abstract
A majority of Parkinson's disease patients had insufficient levels of vitamin D. Parkinson’s disease (PD) is the second most common form of neurodegeneration in the elderly population. In PD, one's levels of dopamine are lowered because the nerve cells which make the chemical have either died or lost their usual functioning. Clinically, it is characterized by tremor, rigidity, slowness of movement, and postural imbalance. The correlation located in vitamin D deficiency can cause PD, or PD can cause vitamin D deficiency. A significant association between low serum vitamin D and PD has been demonstrated, suggesting that elevated vitamin D levels might provide neuroprotection against PD. An evidence suggests that vitamin D supplementation may be beneficial for PD patients.
Key word: Parkinson’s Disease, vitamin D, neurodegeneration, and neuroprotection.
Introduction
Parkinson’s disease (PD) is a movement disorder characterized by tremor, rigidity, slowness of movement, and postural imbalance. …show more content…
Vitamin D insufficiency is a common health problem in elderly individuals, who also have a high prevalence of neurodegenerative diseases. Vitamin D is primarily produced in the skin on exposure to UV-B radiation and is found in limited food sources.(1) ; advancing age, obesity, avoidance of sun exposure, residence in northerly latitudes, and darker skin pigmentation are associated with increased risk of vitamin D deficiency. Patients with chronic neurodegenerative diseases frequently have many risk factors for vitamin D insufficiency.
The vitamin D receptors and an enzyme responsible for the formation of the active form 1,25-hydroxyvitamin D have been found in high levels in the substantia nigra, the region of the brain affected most by Parkinson disease.(2) This raises the possibility that chronic inadequacy of vitamin D leads to the loss of dopaminergic neurons in the substantia nigra region and further Parkinson disease.
Genetic studies have helped identify a number of proteins linking vitamin D to PD pathology, including the the vitamin D receptor (VDR), nerve growth factor (NGF), prostaglandins (PGs), cyclooxygenase-2 (COX-2), also in PD with diabetes mellitus patients and PD patients with osteoporosis.(1)
There is evidence of abnormalities in the vitamin D-endocrine system in PD patients, including low bone mineral density (BMD), and decreased vitamin D levels. These factors, combined with balance problems, are the probable reasons for the high incidence of fractures, especially of the hip, reported in elderly women with PD3. Sunlight exposure can increase the BMD of PD by increasing serum 25-hydroxyvitamin D3 (25OHD) levels.(3) In another study, serum 25OHD and BMD were reported to be reduced in PD patients. Despite an abundance of correlational studies, it is unknown whether vitamin D deficiency is a cause or consequence of PD.
In the literature review will discuss about the role of vitamin D in the Parkinson’s Disease (PD). The cause(s) of PD until now is still unknown, many studies suggest that genetic and environmental both can cause PD, and the newest study suggest there is other factor such as vitamin D that have role in PD pathology, the study about role of vitamin D is still in progress and need more for further investigation about it. The literature review discuss is about result of cohort study compared with in vitro PD induced in mammals study.
Parkinson’s Disease
Parkinson's disease is a disorder of the brain that leads to shaking (tremors) and difficulty with walking, movement, and coordination. Nerve cells use a brain chemical called dopamine to help control muscle movement. Parkinson's disease occurs when the nerve cells in the brain that make dopamine are slowly destroyed. Without dopamine, the nerve cells in that part of the brain cannot properly send messages. This leads to the loss of muscle function. The damage gets worse with time. Exactly why these brain cells waste away is unknown.(4)
Parkinson's disease is caused by a loss of nerve cells in the part of the brain called the substantia nigra.
Nerve cells in this part of the brain are responsible for producing a chemical called dopamine. Dopamine acts as a messenger between the brain and the nervous system, and helps control and co-ordinate body movements. If these nerve cells become damaged or die, the amount of dopamine in the brain is reduced. This means that the part of the brain controlling movement cannot work so well, which causes movements to become slow and abnormal. The loss of nerve cells is a slow process. The level of dopamine in the brain falls over time. Only when 80% of the nerve cells in the substantia nigra have been lost will the symptoms of Parkinson's disease appear and gradually become more
severe.(5)
Parkinson's disease affects nerve cells in several parts of the brain, particularly those that use the chemical messenger dopamine to control movement. The most common symptoms are tremor, stiffness and slowness of movement. These can be treated with oral replacement of dopamine.(4)
The 3 key signs of Parkinson's disease are tremor (shaking) at rest, rigidity, and slowness in the initiation of movement (called bradykinesia). Of these features, 2 are required to make the diagnosis. Postural instability is the fourth key sign, but it happens late in the disease, usually after having PD 8 years or more.(6)
Medications can help you manage problems with walking, movement and tremor by increasing your brain's supply of dopamine. However, dopamine can't be given directly, as it can't enter your brain.
You may have significant improvement of your symptoms after beginning Parkinson's disease treatment. Over time, however, the benefits of drugs frequently diminish or become less consistent, although symptoms usually can continue to be fairly well controlled. The drugs that used for medication include: Levodopa, dopamine agonist, MAO inhibitors, COMT inhibitors, anticholinergic, and amantadine.(6)
Vitamin D
Vitamin D is synthesized in skin by exposure to sunlight (ultraviolet radiation) and obtained in the diet. Vitamin D is a prohormone with several active metabolites that act as hormones. Vitamin D3 is metabolized by the liver to 25(OH)D, which is then converted by the kidneys to 1,25(OH)2D (1,25-dihydroxycholecalciferol, calcitriol, or active vitamin D hormone). 25(OH)D, the major circulating form, has some metabolic activity, but 1,25(OH)2D is the most metabolically active.(7)
Laboratory analysis of Vitamin D concentration Stored plasma samples were analyzed with an enzyme-linked immunosorbent assay kit for 25(OH)D. The limit of detection is 2 ng/mL. SI defined vitamin D insufficiency as a 25(OH)D concentration of 30 ng/mL or less and vitamin D deficiency as a 25(OH)D concentration of less than 20 ng/mL.(8)
Lower than normal levels suggest a vitamin D deficiency. This condition can result from.(8) * Lack of exposure to sunlight * Lack of adequate vitamin D in the diet * Liver and kidney diseases * Malabsorption * Use of certain medicines, including phenytoin, phenobarbital, and rifampin
Role of Vitamin D in Parkinson’s Disease (PD)
Previous studies have shown that the part of the brain affected most by Parkinson's, the substantia nigra, has high levels of the vitamin D receptor, which suggests vitamin D may be important for normal functions of these cells.
This is the correlation between vitamin D and Parkinson’s Disease: 1. Vitamin D Receptor (VDR)
There is sample evidence for vitamin D involvement in mammalian brain function. VDR and 1α-hydroxylase, the enzyme responsible for the formation of active vitamin D in the human brain, are found in the large neurons of the SN.(9) VDR, a nuclear receptor, is restricted to the nucleus but 1α-hydroxylase is distributed throughout the cytoplasm. The presence of these proteins in the CNS suggests that vitamin D is active within the brain. Genetic studies provide an opportunity to link molecular variations with epidemiological data, DNA sequence variations, such as polymorphisms, exert subtle biological effects on the expression and functionality of proteins. VDR mRNA was identified as a potential blood marker for PD. In a Korean population, the VDR BsmI genotype is reported to be associated with PD.(10) Reported that the VDR gene is a potential susceptibility gene for PD in the Caucasian population. These reports suggested a role of vitamin D in PD. 2. Diabetes Mellitus
Glucose is the molecule necessary to produce energy in the brain. A link between DM and PD has been suggested in several reports, but the results have been inconsistent. Insulin receptors and their mRNAs are localized in the SN.(11) A high incidence of abnormal glucose tolerance has been reported in PD. Human and experimental animal studies, however, demonstrated neurodegeneration associated with peripheral insulin resistance.(12) In a 6-OHDA model of PD, striatal insulin resistance was observed in the striatum, and patients with PD exhibited increased autoimmune reactivity to insulin. Individuals newly diagnosed with PD display reduced insulin-mediated glucose uptake, which is hypothesized to be due to inhibit early insulin secretion and hyperglycemia after glucose loading. Furthermore, chronic hyperglycemia decreased limbic extracellular dopamine concentrations and striatal dopaminergic transmission in streptozotocin-induced diabetic rats. Vitamin D levels may provide a link between the diseases; serum 1,25OHD and 25OHD levels are low in diabetic patients, and diabetic rats had an increased metabolic clearance rate of 1,25OHD. Interestingly, a significant high prevalence of vitamin D insufficiency is reported in patients with PD.(13) 3. Nerve Growth Factor (NGF)
NGF is a small secreted protein that is important for the growth, maintenance, and survival of certain target neurons. NGF has been implicated in maintaining and regulating the septohippocampal pathway, which is involved in learning and memory.(14) NGF is also present in the human SN and in the adrenal gland. NGF concentrations are decreased in the SN of the PD and in a rat model of PD. NGF levels showed greater reductions in early states of the disease compared with advanced stages, implying that decreased NGF may be involved in the pathogenesis of PD. NGF is reported to protect dopamine neurotoxicity induced by MPTP, rotenone, and 6-OHDA via different pathways. The chronic infusion of NGF into the rat striatum resulted in cholinergic hyperinnervation and reduced spontaneous activity of striatal neurons. Moreover, NGF increases survival of dopaminergic grafts, rescues nigral dopaminergic neurons, and restores motor dysfunction in a rat model of PD. In addition, the brains of newborn rats from vitamin D-deficient dams showed reduced expression of NGF. In vitro, calcitriol regulated the expression of the VDR gene and stimulated the expression of the NGF gene in Schwann cells. In mouse fibroblasts, calcitriol and vitamin D analogs are reported to enhance NGF induction by increasing AP-1 binding activity to the NGF promoter.(15) These findings suggest a protective role for vitamin D in the CNS.
4. Prostaglandin (PG)
PGs play a role in inflammatory processes. Cyclooxygenase (COX) participates in the conversion of arachidonic acid into PGs. PGE2 is a key product of COX-2 and is increased in the SN of patients with PD and MPTP-induced PD in an animal model. PGE2 is also directly and selectively toxic to dopaminergic neurons.(16) PGE2 receptors are found on dopaminergic neurons in the rat SN. Overexpression of COX-2 is reported in PD and an MPTP-animal model. COX inhibitors provide neuroprotection in the MPTP-mouse model of PD. Similarly, regular use of COX-2 inhibiting nonsteroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen, has been associated with a decreased incidence of PD.(17) Calcitriol, which reportedly regulates the expression of several key genes involved in PG pathways, decreases PG synthesis. Calcitriol and its analogues have also been shown to inhibit selectively the activity of COX-2.(18) These findings suggested that vitamin D has a role in anti-inflammatory processes in PD. 5. Bone Densitometry
The findings show that the bone mineral density (BMD) of all PD patients was significantly lower compared to controls. PD patients had significantly reduced physical and mental performance and more falls and/or fractures in comparison to healthy controls, decreased vitamin D levels, Vitamin D helps the body absorb calcium. Calcium and phosphate are two minerals that are essential for normal bone formation. Vitamin D deficiency among the elderly is quite common in the US. In a study of hospitalized patients in a general medical ward, vitamin D deficiency was detected in 57% of the patients. An estimated 50% of elderly women consume far less vitamin D in their diet than recommended.(19)
Prevalence of vitamin D insufficiency in patients with Parkinson disease (PD), patients with Alzheimer disease (AD), and matched healthy controls.1
Figure 1: Statistical Analysis.
However, the lower vitamin D levels in the PD vs AD cohort are intriguing. The typical course of AD is shorter than that of PD, and PD patients experience mobility problems more frequently than AD patients. Both factors could make a PD patient less likely to get sun exposure and account for the higher prevalence of vitamin D insufficiency.
Conclusion
Recent studies have highlighted a possible relationship between vitamin D and PD. Genetic studies have provided opportunities to determine what proteins may link vitamin D to PD pathology. We know that PD patients have a higher prevalence of vitamin D insufficiency compared with patients with AD and healthy controls. These findings need for further studies to assess what contribution a low 25(OH)D concentration adds to the risk of developing PD, and to determine whether correction of vitamin D insufficiency and deficiency will improve motor or nonmotor symptoms in PD. It is premature to conclude that lack of vitamin D is a precursor to the development of Parkinson's Disease. In fact, between the two factors, we cannot even be clear about which is the cause and which is the consequence. For example, people with restricted movements would largely be confined to indoor areas, and the subsequent lack of sun exposure could then have caused their vitamin D insufficiency. In fact, the connection could even work both ways.
REFERENCE 1. Evatt ML, DeLong MR, Khazai N, et al. Prevalence of Vitamin D Insufficiency in Patients With Parkinson Disease and Alzheimer Disease. Archive Neurology JAMA. 2008;65(10):1348-1352. 2. Knekt P, Kilkkinen A, Rissanen A, et al. Serum Vitamin D and the Risk of Parkinson Disease. Archive Neurology JAMA. Arch Neurol. 2010;67(7):808-811. 3. B. Lorefält, G. Toss, and A.-K. Granérus, “Bone mass in elderly patients with Parkinson's disease,” Acta Neurologica Scandinavica, vol. 116, no. 4, pp. 248–254, 2007. 4. Weaver FM, Follett K, Stern M, et al. Bilateral deep brain stimulation vs best medical therapy for patients with advanced Parkinson disease: a randomized controlled trial. JAMA. 2009;301(1):63-73. 5. National Institute of Health. Parkinson's disease: Hope through research. National Institute of Neurological Disorders and Stroke. 7th of June 2012. 6. Vieth R, et al. The urgent need to recommend an intake of vitamin D that is effective. American Journal of Clinical Nutrition, Vol. 85, No. 3, 649-650, March 2007. 7. Weng FL, Shults J, Leonard MB, Stallings VA, Zemel BS. Risk factors for low serum 25-hydroxyvitamin D concentrations in otherwise healthy children and adolescents. Am J Clin Nutr. 2007;86(1):150-158. 8. D. W. Eyles, S. Smith, R. Kinobe, M. Hewison, and J. J. McGrath, “Distribution of the Vitamin D receptor and 1α-hydroxylase in human brain,” Journal of Chemical Neuroanatomy, vol. 29, no. 1, pp. 21–30, 2005. 9. J. S. Kim, Y. I. Kim, C. Song et al., “Association of vitamin D receptor gene polymorphism and Parkinson's disease in Koreans,” Journal of Korean Medical Science, vol. 20, no. 3, pp. 495–498, 2005. 10. D. P. Figlewicz, S. B. Evans, J. Murphy, M. Hoen, and D. G. Baskin, “Expression of receptors for insulin and leptin in the ventral tegmental area/substantia nigra (VTA/SN) of the rat,” Brain Research, vol. 964, no. 1, pp. 107–115, 2003. 11. M. A. Fishel, G. S. Watson, T. J. Montine et al., “Hyperinsulinemia provokes synchronous increases in central inflammation and β-amyloid in normal adults,” Archives of Neurology, vol. 62, no. 10, pp. 1539–1544, 2005. 12. L. Derex and P. Trouillas, “Reversible Parkinsonism, hypophosphoremia, and hypocalcemia under vitamin D therapy: case report,” Movement Disorders, vol. 12, no. 4, pp. 612–613, 2007. 13. C. W. K. Wu and H. H. Yeh, “Nerve growth factor rapidly increases muscarinic tone in mouse medial septum/diagonal band of Broca,” Journal of Neuroscience, vol. 25, no. 17, pp. 4232–4242, 2005. 14. I. M. Musiol and D. Feldman, “1,25-dihydroxyvitamin D3 induction of nerve growth factor in L929 mouse fibroblasts: effect of vitamin D receptor regulation and potency of vitamin D3 analogs,” Endocrinology, vol. 138, no. 1, pp. 12–18, 2007. 15. E. Carrasco, D. Casper, and P. Werner, “PGE2 receptor EP1 renders dopaminergic neurons selectively vulnerable to low-level oxidative stress and direct PGE2 neurotoxicity,” Journal of Neuroscience Research, vol. 85, no. 14, pp. 3109–3117, 2007. 16. H. Chen, S. M. Zhang, M. A. Hernán et al., “Nonsteroidal anti-inflammatory drugs and the risk of Parkinson disease,” Archives of Neurology, vol. 60, no. 8, pp. 1059–1064, 2003. 17. R. Aparna, J. Subhashini, K. R. Roy et al., “Selective inhibition of cyclooxygenase-2 (COX-2) by 1 α,25-dihydroxy- 16-ene-23-yne-vitamin D3, a less calcemic vitamin D analog,” Journal of Cellular Biochemistry, vol. 104, no. 5, pp. 1832–1842, 2008. 18. S. Abou-Raya, M. Helmii, and A. Abou-Raya, “Bone and mineral metabolism in older adults with Parkinson's disease,” Age and Ageing, vol. 38, no. 6, pp. 675–680, 2009.
Trisakti University of Medicine
I Made Setiadji
030.09.114
Jakarta, June 14th 2012
Abstract
A majority of Parkinson's disease patients had insufficient levels of vitamin D. Parkinson’s disease (PD) is the second most common form of neurodegeneration in the elderly population. In PD, one's levels of dopamine are lowered because the nerve cells which make the chemical have either died or lost their usual functioning. Clinically, it is characterized by tremor, rigidity, slowness of movement, and postural imbalance. The correlation located in vitamin D deficiency can cause PD, or PD can cause vitamin D deficiency. A significant association between low serum vitamin D and PD has been demonstrated, suggesting that elevated vitamin D levels might provide neuroprotection against PD. An evidence suggests that vitamin D supplementation may be beneficial for PD patients.
Key word: Parkinson’s Disease, vitamin D, neurodegeneration, and neuroprotection.
Introduction
Parkinson’s disease (PD) is a movement disorder characterized by tremor, rigidity, slowness of movement, and postural imbalance. …show more content…
Vitamin D insufficiency is a common health problem in elderly individuals, who also have a high prevalence of neurodegenerative diseases. Vitamin D is primarily produced in the skin on exposure to UV-B radiation and is found in limited food sources.(1) ; advancing age, obesity, avoidance of sun exposure, residence in northerly latitudes, and darker skin pigmentation are associated with increased risk of vitamin D deficiency. Patients with chronic neurodegenerative diseases frequently have many risk factors for vitamin D insufficiency.
The vitamin D receptors and an enzyme responsible for the formation of the active form 1,25-hydroxyvitamin D have been found in high levels in the substantia nigra, the region of the brain affected most by Parkinson disease.(2) This raises the possibility that chronic inadequacy of vitamin D leads to the loss of dopaminergic neurons in the substantia nigra region and further Parkinson disease.
Genetic studies have helped identify a number of proteins linking vitamin D to PD pathology, including the the vitamin D receptor (VDR), nerve growth factor (NGF), prostaglandins (PGs), cyclooxygenase-2 (COX-2), also in PD with diabetes mellitus patients and PD patients with osteoporosis.(1)
There is evidence of abnormalities in the vitamin D-endocrine system in PD patients, including low bone mineral density (BMD), and decreased vitamin D levels. These factors, combined with balance problems, are the probable reasons for the high incidence of fractures, especially of the hip, reported in elderly women with PD3. Sunlight exposure can increase the BMD of PD by increasing serum 25-hydroxyvitamin D3 (25OHD) levels.(3) In another study, serum 25OHD and BMD were reported to be reduced in PD patients. Despite an abundance of correlational studies, it is unknown whether vitamin D deficiency is a cause or consequence of PD.
In the literature review will discuss about the role of vitamin D in the Parkinson’s Disease (PD). The cause(s) of PD until now is still unknown, many studies suggest that genetic and environmental both can cause PD, and the newest study suggest there is other factor such as vitamin D that have role in PD pathology, the study about role of vitamin D is still in progress and need more for further investigation about it. The literature review discuss is about result of cohort study compared with in vitro PD induced in mammals study.
Parkinson’s Disease
Parkinson's disease is a disorder of the brain that leads to shaking (tremors) and difficulty with walking, movement, and coordination. Nerve cells use a brain chemical called dopamine to help control muscle movement. Parkinson's disease occurs when the nerve cells in the brain that make dopamine are slowly destroyed. Without dopamine, the nerve cells in that part of the brain cannot properly send messages. This leads to the loss of muscle function. The damage gets worse with time. Exactly why these brain cells waste away is unknown.(4)
Parkinson's disease is caused by a loss of nerve cells in the part of the brain called the substantia nigra.
Nerve cells in this part of the brain are responsible for producing a chemical called dopamine. Dopamine acts as a messenger between the brain and the nervous system, and helps control and co-ordinate body movements. If these nerve cells become damaged or die, the amount of dopamine in the brain is reduced. This means that the part of the brain controlling movement cannot work so well, which causes movements to become slow and abnormal. The loss of nerve cells is a slow process. The level of dopamine in the brain falls over time. Only when 80% of the nerve cells in the substantia nigra have been lost will the symptoms of Parkinson's disease appear and gradually become more
severe.(5)
Parkinson's disease affects nerve cells in several parts of the brain, particularly those that use the chemical messenger dopamine to control movement. The most common symptoms are tremor, stiffness and slowness of movement. These can be treated with oral replacement of dopamine.(4)
The 3 key signs of Parkinson's disease are tremor (shaking) at rest, rigidity, and slowness in the initiation of movement (called bradykinesia). Of these features, 2 are required to make the diagnosis. Postural instability is the fourth key sign, but it happens late in the disease, usually after having PD 8 years or more.(6)
Medications can help you manage problems with walking, movement and tremor by increasing your brain's supply of dopamine. However, dopamine can't be given directly, as it can't enter your brain.
You may have significant improvement of your symptoms after beginning Parkinson's disease treatment. Over time, however, the benefits of drugs frequently diminish or become less consistent, although symptoms usually can continue to be fairly well controlled. The drugs that used for medication include: Levodopa, dopamine agonist, MAO inhibitors, COMT inhibitors, anticholinergic, and amantadine.(6)
Vitamin D
Vitamin D is synthesized in skin by exposure to sunlight (ultraviolet radiation) and obtained in the diet. Vitamin D is a prohormone with several active metabolites that act as hormones. Vitamin D3 is metabolized by the liver to 25(OH)D, which is then converted by the kidneys to 1,25(OH)2D (1,25-dihydroxycholecalciferol, calcitriol, or active vitamin D hormone). 25(OH)D, the major circulating form, has some metabolic activity, but 1,25(OH)2D is the most metabolically active.(7)
Laboratory analysis of Vitamin D concentration Stored plasma samples were analyzed with an enzyme-linked immunosorbent assay kit for 25(OH)D. The limit of detection is 2 ng/mL. SI defined vitamin D insufficiency as a 25(OH)D concentration of 30 ng/mL or less and vitamin D deficiency as a 25(OH)D concentration of less than 20 ng/mL.(8)
Lower than normal levels suggest a vitamin D deficiency. This condition can result from.(8) * Lack of exposure to sunlight * Lack of adequate vitamin D in the diet * Liver and kidney diseases * Malabsorption * Use of certain medicines, including phenytoin, phenobarbital, and rifampin
Role of Vitamin D in Parkinson’s Disease (PD)
Previous studies have shown that the part of the brain affected most by Parkinson's, the substantia nigra, has high levels of the vitamin D receptor, which suggests vitamin D may be important for normal functions of these cells.
This is the correlation between vitamin D and Parkinson’s Disease: 1. Vitamin D Receptor (VDR)
There is sample evidence for vitamin D involvement in mammalian brain function. VDR and 1α-hydroxylase, the enzyme responsible for the formation of active vitamin D in the human brain, are found in the large neurons of the SN.(9) VDR, a nuclear receptor, is restricted to the nucleus but 1α-hydroxylase is distributed throughout the cytoplasm. The presence of these proteins in the CNS suggests that vitamin D is active within the brain. Genetic studies provide an opportunity to link molecular variations with epidemiological data, DNA sequence variations, such as polymorphisms, exert subtle biological effects on the expression and functionality of proteins. VDR mRNA was identified as a potential blood marker for PD. In a Korean population, the VDR BsmI genotype is reported to be associated with PD.(10) Reported that the VDR gene is a potential susceptibility gene for PD in the Caucasian population. These reports suggested a role of vitamin D in PD. 2. Diabetes Mellitus
Glucose is the molecule necessary to produce energy in the brain. A link between DM and PD has been suggested in several reports, but the results have been inconsistent. Insulin receptors and their mRNAs are localized in the SN.(11) A high incidence of abnormal glucose tolerance has been reported in PD. Human and experimental animal studies, however, demonstrated neurodegeneration associated with peripheral insulin resistance.(12) In a 6-OHDA model of PD, striatal insulin resistance was observed in the striatum, and patients with PD exhibited increased autoimmune reactivity to insulin. Individuals newly diagnosed with PD display reduced insulin-mediated glucose uptake, which is hypothesized to be due to inhibit early insulin secretion and hyperglycemia after glucose loading. Furthermore, chronic hyperglycemia decreased limbic extracellular dopamine concentrations and striatal dopaminergic transmission in streptozotocin-induced diabetic rats. Vitamin D levels may provide a link between the diseases; serum 1,25OHD and 25OHD levels are low in diabetic patients, and diabetic rats had an increased metabolic clearance rate of 1,25OHD. Interestingly, a significant high prevalence of vitamin D insufficiency is reported in patients with PD.(13) 3. Nerve Growth Factor (NGF)
NGF is a small secreted protein that is important for the growth, maintenance, and survival of certain target neurons. NGF has been implicated in maintaining and regulating the septohippocampal pathway, which is involved in learning and memory.(14) NGF is also present in the human SN and in the adrenal gland. NGF concentrations are decreased in the SN of the PD and in a rat model of PD. NGF levels showed greater reductions in early states of the disease compared with advanced stages, implying that decreased NGF may be involved in the pathogenesis of PD. NGF is reported to protect dopamine neurotoxicity induced by MPTP, rotenone, and 6-OHDA via different pathways. The chronic infusion of NGF into the rat striatum resulted in cholinergic hyperinnervation and reduced spontaneous activity of striatal neurons. Moreover, NGF increases survival of dopaminergic grafts, rescues nigral dopaminergic neurons, and restores motor dysfunction in a rat model of PD. In addition, the brains of newborn rats from vitamin D-deficient dams showed reduced expression of NGF. In vitro, calcitriol regulated the expression of the VDR gene and stimulated the expression of the NGF gene in Schwann cells. In mouse fibroblasts, calcitriol and vitamin D analogs are reported to enhance NGF induction by increasing AP-1 binding activity to the NGF promoter.(15) These findings suggest a protective role for vitamin D in the CNS.
4. Prostaglandin (PG)
PGs play a role in inflammatory processes. Cyclooxygenase (COX) participates in the conversion of arachidonic acid into PGs. PGE2 is a key product of COX-2 and is increased in the SN of patients with PD and MPTP-induced PD in an animal model. PGE2 is also directly and selectively toxic to dopaminergic neurons.(16) PGE2 receptors are found on dopaminergic neurons in the rat SN. Overexpression of COX-2 is reported in PD and an MPTP-animal model. COX inhibitors provide neuroprotection in the MPTP-mouse model of PD. Similarly, regular use of COX-2 inhibiting nonsteroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen, has been associated with a decreased incidence of PD.(17) Calcitriol, which reportedly regulates the expression of several key genes involved in PG pathways, decreases PG synthesis. Calcitriol and its analogues have also been shown to inhibit selectively the activity of COX-2.(18) These findings suggested that vitamin D has a role in anti-inflammatory processes in PD. 5. Bone Densitometry
The findings show that the bone mineral density (BMD) of all PD patients was significantly lower compared to controls. PD patients had significantly reduced physical and mental performance and more falls and/or fractures in comparison to healthy controls, decreased vitamin D levels, Vitamin D helps the body absorb calcium. Calcium and phosphate are two minerals that are essential for normal bone formation. Vitamin D deficiency among the elderly is quite common in the US. In a study of hospitalized patients in a general medical ward, vitamin D deficiency was detected in 57% of the patients. An estimated 50% of elderly women consume far less vitamin D in their diet than recommended.(19)
Prevalence of vitamin D insufficiency in patients with Parkinson disease (PD), patients with Alzheimer disease (AD), and matched healthy controls.1
Figure 1: Statistical Analysis.
However, the lower vitamin D levels in the PD vs AD cohort are intriguing. The typical course of AD is shorter than that of PD, and PD patients experience mobility problems more frequently than AD patients. Both factors could make a PD patient less likely to get sun exposure and account for the higher prevalence of vitamin D insufficiency.
Conclusion
Recent studies have highlighted a possible relationship between vitamin D and PD. Genetic studies have provided opportunities to determine what proteins may link vitamin D to PD pathology. We know that PD patients have a higher prevalence of vitamin D insufficiency compared with patients with AD and healthy controls. These findings need for further studies to assess what contribution a low 25(OH)D concentration adds to the risk of developing PD, and to determine whether correction of vitamin D insufficiency and deficiency will improve motor or nonmotor symptoms in PD. It is premature to conclude that lack of vitamin D is a precursor to the development of Parkinson's Disease. In fact, between the two factors, we cannot even be clear about which is the cause and which is the consequence. For example, people with restricted movements would largely be confined to indoor areas, and the subsequent lack of sun exposure could then have caused their vitamin D insufficiency. In fact, the connection could even work both ways.
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