Progress 10/01/03 to 09/30/04
Outputs
This study investigated the relationships between vitamin D deficiency and auditory function in mice that vary in their genetic vulnerability to hearing loss from none to severe. We have completed several experiments on one mouse strain that serves as the normal hearing standard (CBA/CaJ) and 3 other strains varying in their genetic susceptibility to hearing loss (DBA/2J, C57BL/6J, and BALB/c). We also examined the combined effects of vitamin D and calcium deficiency in the BALB/c strain. Results from blood assays showed markedly lower serum 25-hydroxyvitamin D (serum 25- OH-D) levels in mice on the vitamin D deficient diets (serum 25-OH-D < 5 ng/ml), regardless of strain. Initially, we obtained mice in lactating stages and began hearing assessments via auditory brainstem recordings (ABR) shortly after weaning. Thresholds were measured at five test frequencies 4, 8, 16, 24, 32 kHz. Results showed slightly abnormal thresholds in BALB/c, but not in the other strains. We
repeated this experiment exactly as the first and again found mildly accelerated hearing loss in the BALB/c, and CBA/Ca (after extended weeks on the diet), but not the C57BL/6 or the DBA mice; thus, we eliminated those two groups from the study. Although blood assays showed low serum 25-hydroxyvitamin D concentrations, there are no published reports on how low these levels must be in a mouse to be truly deficient and because growth charts for the mice on the nutrient deficient diet as well as the control diet were virtually identical, an effort was made to make the mouse more deficient by adding a calcium (Ca) deficiency. We repeated the above experimental paradigm again, but this time mice received either a control diet or one lacking in vitamin D and one of three levels of Ca deficiency (0.2%, 0.1%, & 0.05%). Mild differences were found in the very high frequencies between the control group and the mice consuming the vitamin D and 0.05% Ca diet. Our final experiments included the
same vitamin D and Ca diets, but this time the pregnant females we fed the diets beginning at 14 days of pregnancy. Hearing thresholds were not different in the offspring after weaning. For the BALB/c mice, at one week post weaning hearing thresholds for the deficient diet groups were elevated in comparison to the controls. These differences persisted for the next six weeks (through Week 7) and were significant for several test frequencies; the more severe the diet, the greater the rate of change in thresholds. Mice on the most severe diet (0.1% Ca diet group) showed the greatest change in thresholds; whereas the mice on the 0.2% Ca diet group showed a change in hearing thresholds intermediate among the groups. Differences in hearing thresholds also were observed for the CBA/Ca mice, but this strain was much less affected by the nutritional deficiency. In conclusion, we found that vitamin D and Ca deficiency accelerates hearing loss in some mouse strains. Our next step is to determine
the mechanism responsible for these changes through histological studies.
Impacts
Identification of nutritional factors that affect hearing sensitivity has the potential to improve the quality of life for millions of people throughout the life span. The implication is that diet and other interventions may reduce the incidence of hearing impairment.If we identify nutritional factors associated with hearing loss, then there is potential that diet and other interventions throughout the life cycle will decrease the incidence of hearing impairment; thereby,improving quality of life.
Publications
- Park, S, De Chicchis, A, Marseli, H, Johnson, MA, Willott, J (March, 2004). Calcium and Vitamin D Deficiency Impair Auditory Function in Mice. AAS Bulletin, 29 (1), 42. De Chicchis, AR, Johnson, MA, Park, S, Marseli, H, Willott, J (2003). Nutrient deficiency and auditory function in genetically disordered mice. AAS Bulletin, 28 (1), 29.
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Progress 10/01/03 to 08/31/04
Outputs
Target Audience:nullChanges/Problems:nullWhat opportunities for training and professional development has the project provided?This study investigated the relationships between vitamin D deficiency and auditory function in mice that vary in their genetic vulnerability to hearing loss from none to severe. We have completed several experiments on one mouse strain that serves as the normal hearing standard (CBA/CaJ) and 3 other strains varying in their genetic susceptibility to hearing loss (DBA/2J, C57BL/6J, and BALB/c). We also examined the combined effects of vitamin D and calcium deficiency in the BALB/c strain. Results from blood assays showed markedly lower serum 25-hydroxyvitamin D (serum 25- OH-D) levels in mice on the vitamin D deficient diets (serum 25-OH-D < 5 ng/ml), regardless of strain. Initially, we obtained mice in lactating stages and began hearing assessments via auditory brainstem recordings (ABR) shortly after weaning. Thresholds were measured at five test frequencies 4, 8, 16, 24, 32 kHz. Results showed slightly abnormal thresholds in BALB/c, but not in the other strains. We
repeated this experiment exactly as the first and again found mildly accelerated hearing loss in the BALB/c, and CBA/Ca (after extended weeks on the diet), but not the C57BL/6 or the DBA mice; thus, we eliminated those two groups from the study. Although blood assays showed low serum 25-hydroxyvitamin D concentrations, there are no published reports on how low these levels must be in a mouse to be truly deficient and because growth charts for the mice on the nutrient deficient diet as well as the control diet were virtually identical, an effort was made to make the mouse more deficient by adding a calcium (Ca) deficiency. We repeated the above experimental paradigm again, but this time mice received either a control diet or one lacking in vitamin D and one of three levels of Ca deficiency (0.2%, 0.1%, & 0.05%). Mild differences were found in the very high frequencies between the control group and the mice consuming the vitamin D and 0.05% Ca diet. Our final experiments included the
same vitamin D and Ca diets, but this time the pregnant females we fed the diets beginning at 14 days of pregnancy. Hearing thresholds were not different in the offspring after weaning. For the BALB/c mice, at one week post weaning hearing thresholds for the deficient diet groups were elevated in comparison to the controls. These differences persisted for the next six weeks (through Week 7) and were significant for several test frequencies; the more severe the diet, the greater the rate of change in thresholds. Mice on the most severe diet (0.1% Ca diet group) showed the greatest change in thresholds; whereas the mice on the 0.2% Ca diet group showed a change in hearing thresholds intermediate among the groups. Differences in hearing thresholds also were observed for the CBA/Ca mice, but this strain was much less affected by the nutritional deficiency. In conclusion, we found that vitamin D and Ca deficiency accelerates hearing loss in some mouse strains. Our next step is to determine
the mechanism responsible for these changes through histological studies.How have the results been disseminated to communities of interest?nullWhat do you plan to do during the next reporting period to accomplish the goals?null
Impacts
What was accomplished under these goals?
Identification of nutritional factors that affect hearing sensitivity has the potential to improve the quality of life for millions of people throughout the life span. The implication is that diet and other interventions may reduce the incidence of hearing impairment.If we identify nutritional factors associated with hearing loss, then there is potential that diet and other interventions throughout the life cycle will decrease the incidence of hearing impairment; thereby,improving quality of life.
Publications
- Citation:
Park, S, De Chicchis, A, Marseli, H, Johnson, MA, Willott, J (March, 2004). Calcium and Vitamin D Deficiency Impair Auditory Function in Mice. AAS Bulletin, 29 (1), 42. De Chicchis, AR, Johnson, MA, Park, S, Marseli, H, Willott, J (2003). Nutrient deficiency and auditory function in genetically disordered mice. AAS Bulletin, 28 (1), 29.
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Progress 10/01/02 to 09/30/03
Outputs
This study is investigating the relationships between vitamin D deficiency and auditory function in mice that vary in their genetic vulnerability to hearing loss from none to severe .We proposed to study four mouse strains: 1) CBA, 2) DBA/2J, 3) C57BL/6J, and 4) BALB/c. Results show markedly lower serum 25-hydroxyvitamin D (serum 25- OH-D) and phosphorus levels in mice on the vitamin D deficient diets had 25-OH-D (< 5 ng/ml), regardless of strain. Hearing thresholds have been assessed on all four mouse strains. Preliminary findings indicate that vitamin D deficiency does not appear to influence hearing sensitivity to any significant degree in the DBA/2J strain. This may be because hearing loss in this strain is so severe and occurs at such a rapid rate. Similarly, no significant effects of vitamin D deficiency was found in the C57BL strain either. BALB/c findings were more encouraging. In this strain, we found accelerated hearing thresholds compared to the control
group being fed a normal purified diet. These findings began to emerge around 2-3 weeks and persisted for several weeks. It appears that in this strain, vitamin D deficiency was associated with a mild and transient hearing loss because after several weeks, hearing sensitivities were no longer related to vitamin D status. We speculate that the apparent mild and transient hearing impairment seen with vitamin D deficiency to date may be in part related to creating only a mild vitamin D deficiency. In an effort to develop a more deficient model, we began a series of experiments where diets low in both calcium and vitamin D are used, as well as creating vitamin D deficiency in utero. In the first of these experiments, we collected data on 4 groups of BALB/c. One group received a vitamin D deficient diet only, and a second group was fed a purified diet only. The remaining 2 groups received a vitamin D deficient diet for 4-5 weeks, at which time some mice were killed and blood drawn to test
for 25-OH-D levels, and the remaining mice were repleted with vitamin D by placing them on the purified diet for 5-6 weeks. In the second experiment, 3 groups of BALB/c mice were placed on a diet deficient of vitamin D and also deficient of calcium (CA = .05, .1 and .2% of normal daily dose). Neither experiment produced statistically significant differences in hearing thresholds. We just began testing 3 more groups of BALB/c bred and weaned from mice who also were fed vitamin D and calcium deficient diets during pregnancy. CBA mice do not develop age-related hearing loss and frequently serve as a normal hearing control. When mice from this stain were fed a vitamin D deficient diet and compared to a control group fed a purified diet, the results showed that the two groups of mice were affected differentially. Although this occurred at several frequencies, the time interval for which it occurred varied across frequency. This may mean that any adverse effects of vitamin D on auditory
function is a generalized phenomenon. Next year we will to continue to analyze these findings as well as collect additional threshold data, to present at meetings and publish our findings.
Impacts
If we identify nutritional factors associated with hearing loss, then there is potential that diet and other interventions throughout the life cycle will decrease the incidence of hearing impairment; thereby,improving quality of life.
Publications
- De Chicchis, A., Johnson, MA, Park, S., Marseli, H. & Willott, J. (March, 2003). Nutrient deficiency and auditory function in genetically disordered mice. Paper presented at the Meeting of the American Auditory Society, Scottsdale, AZ.
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Progress 10/01/01 to 09/30/02
Outputs
This study was designed to investigate the relationships between vitamin D deficiency and auditory function in mice that vary in their genetic vulnerability to hearing loss from none to severe .We proposed to study four mouse strains: 1) CBA, 2) DBA/2J, 3) C57BL/6J, and 4) BALB/c. Results show markedly lower serum 25-hydroxyvitamin D (serum 25- OH-D) and phosphorus levels in mice on the vitamin D deficient diets(< 5 ng/ml), regardless of strain. Hearing thresholds have been assessed on all four mouse strains. Preliminary findings indicate that vitamin D deficiency does not appear to influence hearing sensitivity to any significant degree in the DBA/2J strain. This may be because hearing loss in this strain is so severe and occurs at such a rapid rate. Similarly, no significant effects of vitamin D deficiency was found on the hearing sensitivity of the C57BL strain either. BALB/c findings were more encouraging. In this strain, we found accelerated hearing thresholds
compared to the control group being fed a normal purified diet. These findings began to emerge around 2-3 weeks and persisted for several weeks. It appears that in this strain, vitamin D deficiency was associated with a mild and transient hearing loss because after several weeks, hearing sensitivities were no longer related to vitamin D status. We speculate that the apparent mild and transient hearing impairment seen with vitamin D deficiency to date may be in part related to creating only a mild vitamin D deficiency. In an effort to develop a more deficient model, we began a series of experiments where diets low in both calcium and vitamin D are used, as well as creating vitamin D deficiency in utero. In the first of these experiments, we collected data on 4 groups of BALB/c. One group received a vitamin D deficient diet only, and a second group was fed a purified diet only. The remaining 2 groups received a vitamin D deficient diet for 4-5 weeks, at which time some mice were killed
and blood drawn to test for 25-OH-D levels, and the remaining mice were repleted with vitamin D by placing them on the purified diet for 5-6 weeks. In the second experiment, 3 groups of BALB/c mice were placed on a diet deficient of vitamin D and also deficient of calcium (.1%,.2%,.05% of normal daily dose). Neither experiment produced statistically significant differences in hearing thresholds. We just began testing 3 more groups of BALB/c bred and weaned from mice who also were fed vitamin D and calcium deficient diets during pregnancy. CBA mice do not develop age-related hearing loss and frequently serve as a normal hearing control. When mice from this stain were fed a vitamin D deficient diet and compared to a control group fed a purified diet, the results showed that the two groups of mice were affected differentially. Although this occurred at several frequencies, the time interval for which it occurred varied across frequency. This may mean that any adverse effects of vitamin D
on auditory function is a generalized phenomenon. Next year we will to continue to analyze these findings as well as collect additional threshold data, to present at meetings and publish our findings.
Impacts
If we identify nutritional factors associated with hearing loss, then there is great potential that diet and other interventions throughout the life cycle will decrease the incidence of hearing impairment, and improve quality of life.
Publications
- No publications reported this period
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Progress 10/01/00 to 09/30/01
Outputs
The primary objectives of this investigation are to determine the influence of: 1) vitamin D deficiency on accelerating progressive hearing loss in mice that vary in their genetic vulnerability to age-related auditory dysfunction and 2) vitamin D repletion on the restoration of auditory function following vitamin D deprivation. Much of the time this year was spent training our staff and optimizing both our equipment and our techniques to ensure that our data collection procedures were robust and reproducible. We met with our consultants regularly to ensure that conditions for producing vitamin D deficiency were optimal and our equipment and approach to auditory assessment was optimal. This included discussions with Dr. Hardy Edwards , from The University of Georgia and an expert in vitamin D, regarding our controlled lighting and Dr. James Willott, from the University of South Florida and the Jackson Laboratory, an expert in auditory research with mice. We proposed
investigating the effects of nutritional deficiency on auditory function in four different mouse strains that vary in their genetic vulnerability. Of the four proposed strains, we focused our initial studies the DBA/2J and CBA/CaJ. The DBA/2J mice have severe progressive hearing loss that has an earlier onset and greater sensitivity than any of the mouse strains that we proposed to study. Our initial results indicate that vitamin D deficiency does not appear to have much influence on hearing loss in this mouse strain. This perhaps is due to the fact that their hearing loss is so profound and so rapid. The CBA/CaJ strain does not exhibit age-related hearing loss and is the "standard" for normal hearing in auditory research. Our initial findings in this strain indicate that hearing thresholds are differentially affected in mice fed a vitamin D deficient diet in comparison to a control group of the same strain that is fed a regular purified diet. The effects were seen for four different
frequencies (8000, 16000, 24000 and 32000 Hz), but at different time intervals. We are exploring data from the CBA strain in more detail and will explore other aspects of auditory function such as the amplitude and latency of the auditory brainstem response. The observation that mice without a genetic defect in their auditory function respond adversely to vitamin D deficiency suggests that adverse effects of vitamin D deficiency on auditory function may be a generalized phenomenon. In summary, we have made very good progress in the first year of this study by setting up our auditory and nutrition laboratory, the only one we know of in the U.S., as well as obtaining very useful data from two strains of mice having genetic differences in their auditory function. Further research in the CBA strain as well as additional strains will clarify these relationships further in year two. Finally, serum vitamin D assays should be completed this Fall.
Impacts
If our hypotheses are correct, our findings will lay the foundation for an entirely new area of research that seeks to decrease the risk of hearing impairment through identification of genes associated with hearing loss and their interaction with diet and nutritional status. If we identify nutritional factors associated with hearing loss, then there is great potential that diet and other interventions throughout the life cycle will decrease the incidence of hearing impairment and improve quality of life.
Publications
- No publications reported this period
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