Source: UNIVERSITY OF GEORGIA submitted to
VITAMIN D DEFICIENCY AND AUDITORY FUNCTION OF GENETICALLY DISORDERED MICE
 
PROJECT DIRECTOR: De Chicchis, A. R.
 
PERFORMING ORGANIZATION
COMMUNICATION SCIENCES & DISORDERS
UNIVERSITY OF GEORGIA
ATHENS,GA 30602
 
NON TECHNICAL SUMMARY: Approximately 28 million people in the United States are deaf or hard of hearing. Age-related hearing loss is the most common auditory disorder. Hearing impairment occurs in more than 300 genetic disorders. Our research team has found that nutritional disorders, such as poor vitamin D and calcium status, are associated with age-related hearing impairment in healthy humans as well as in mice with genetic defects in their auditory system. We are the only research team known to be investigating the combined role of nutrition and genetics in age-related hearing loss. We will explore the relationship of vitamin D deficiency with auditory function in four strains of mice that vary in their genetic vulnerability to hearing loss. Our specific objectives are to determine the influence of: 1. Vitamin D deficiency on accelerating the progression of hearing loss in mice with genetic disorders of hearing function. 2. Vitamin D repletion on the restoration of hearing function following vitamin D deficiency. We will study vitamin D depletion and repletion in four strains of mice that vary in their genetic vulnerability to hearing loss from none to severe: CBA/CaJ, C57BL/6J(B6), BALB/c, DBA/2J(D2). We propose that vitamin D-depletion will accelerate hearing loss to the greatest extent in mice with genes for hearing loss, but vitamin D-repletion will only partially restore auditory function following vitamin D deficiency. Our results will provide new insight into the roles of vitamin D and genetics in age-related hearing loss.
 
OBJECTIVES: Our objective is to explore the relationship of vitamin D deficiency with auditory function in four strains of mice that vary in their genetic vulnerability to hearing loss. Specifically, the objectives of this study are to determine the influence of: 1. Vitamin D deficiency on accelerating the progression of hearing loss in mice with genetic disorders of hearing function. 2. Vitamin D repletion on the restoration of hearing function following vitamin D deficiency.
 
APPROACH: Four strains of mice (DBA/2J[D2], CBA/CaJ, C57BL/6J[B6], and BALB/c) will be given either a vitamin D-adequate diet or a vitamin D-deficient diet (n=170). Auditory function will be determined using auditory brainstem response (ABR) measurements, which is a standard procedure for measuring hearing sensitivity in experimental animals. Hearing sensitivity will be monitored approximately once per week for about two months (DBA/2J mice), 3 months (BALB/c mice), and 6 months (CBA/CaJ and C57BL/6J mice). The number of times each strain is tested will vary according to the rate and severity of hearing loss, as well as how quickly vitamin D deficiency causes abnormal ABRs. After auditory function becomes abnormal, the vitamin D-deficient mice will be repleted with the vitamin D-adequate diet.
 
CRIS NUMBER: 0189531 SUBFILE: CRIS
PROJECT NUMBER: GEOR-2001-00556 SPONSOR AGENCY: NIFA
PROJECT TYPE: NRI COMPETITIVE GRANT PROJECT STATUS: EXTENDED MULTI-STATE PROJECT NUMBER: (N/A)
START DATE: Sep 1, 2001 TERMINATION DATE: Aug 31, 2004

GRANT PROGRAM: IMPROVING HUMAN NUTRITION FOR OPTIMAL HEALTH
GRANT PROGRAM AREA: Nitrogen Fixation

CLASSIFICATION
Knowledge Area (KA)Subject (S)Science (F)Objective (G)Percent
702601010105.1100%

CLASSIFICATION HEADINGS
KA702 - Requirements and Function of Nutrients and Other Food Components
S6010 - Individuals
F1010 - Nutrition and metabolism
G5.1 - Ensure Access to Nutritious Food


RESEARCH EFFORT CATEGORIES
BASIC 25%
APPLIED 75%
DEVELOPMENTAL (N/A)%

KEYWORDS: hearing; aging; genetics; vitamin d; human nutrition; animal models; mice; nutrient deficiency; nutrient function; human health; diet; strains (genetics); disease treatment; comparative analysis; sensitivity; monitoring; disease severity; rate determination

PROGRESS: Oct 1, 2003 TO Sep 30, 2004
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.

IMPACT: 2003-10-01 TO 2004-09-30 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.

PUBLICATION INFORMATION: 2003-10-01 TO 2004-09-30
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.

PROJECT CONTACT INFORMATION
NAME: DECHICCHIS, A. R.
PHONE: 706-542-5059
FAX: 706-542-5348