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Grant: Travel Awards - Institute Community Support

Direct Payment

$1,000.00

Embryonic DNA repair and ethanol-initiated behavioural deficits in oxoguanine glycosylase 1 (OGG1) knockout mice: A role of oxidatively damaged DNA and protection by a free radical spin trapping agent

EF 2012-13

Résumé
While it is widely known that alcohol consumption during pregnancy is harmful to the unborn child, the nature of the damage and how it occurs is not known, precluding the identification of high-risk children and potential therapeutic strategies for prevention. Alcohol causes visible physical deformities, but it can also damage the brain, which can affect behaviour including learning, memory and intelligence as the child grows up. These behavioural changes can reduce the quality of the life for these children and their families, with associated indirect costs to society. Among several possible causes, we have examined the possibility that alcohol creates 'free radicals', or highly reactive forms of oxygen, which damage DNA in the developing child causing errors in how their cells and organs are formed and function. To study this, we used mice that were genetically altered so they are unable to fix damaged DNA caused by free radicals, and gave them alcohol during pregnancy. After the mice gave birth, their exposed offspring were tested during adolescence for their ability to perform in a test of learning and memory. Among offspring exposed to alcohol, those that could not fix damaged DNA exhibited more brain damage caused by free radicals, and a decreased ability to learn for months after birth, compared to offspring from the same litter that had normal DNA repair and exhibited normal learning. Moreover, these learning deficits in the DNA repair-deficient offspring occurred at a low dose of alcohol that did not cause physical deformities. When a separate group of pregnant mice were pretreated with an agent that neutralizes or "traps" free radicals, their offspring were protected from both brain damage and the resulting behavioural problems. These results show that alcohol consumption during pregnancy can cause the formation of free radicals, which damage the brain of the developing child, resulting in learning and memory problems later in life.
Programme
Travel Awards - Institute Community Support
Bénéficiaire
Emplacement
Ontario, Canada
Type
Grant
Source
CIHR Funding Decisions Database

Tel que publié

Id
269110
Name
Miller Lutfiya
Region
Ontario
Country
Canada
Orgtype
Research Institution
Instname2
Population and Public Health
Theme2
Biomedical
Prcname2
Institute of Human Development, Child and Youth Health
Projecttitle
Embryonic DNA repair and ethanol-initiated behavioural deficits in oxoguanine glycosylase 1 (OGG1) knockout mice: A role of oxidatively damaged DNA and protection by a free radical spin trapping agent
Programtype2
Undefined
Orgnameinp2
Direct Payment
Cihramount2
$1,000
Cihrequipment2
$0
Programname2
Travel Awards - Institute Community Support
Keyworddelim
Alcohol; Behavioural Deficits; Dna Repair; Fetal Alcohol Spectrum Disorder; Oxidative Stress; Oxidatively Damaged Dna
Abstract
While it is widely known that alcohol consumption during pregnancy is harmful to the unborn child, the nature of the damage and how it occurs is not known, precluding the identification of high-risk children and potential therapeutic strategies for prevention. Alcohol causes visible physical deformities, but it can also damage the brain, which can affect behaviour including learning, memory and intelligence as the child grows up. These behavioural changes can reduce the quality of the life for these children and their families, with associated indirect costs to society. Among several possible causes, we have examined the possibility that alcohol creates 'free radicals', or highly reactive forms of oxygen, which damage DNA in the developing child causing errors in how their cells and organs are formed and function. To study this, we used mice that were genetically altered so they are unable to fix damaged DNA caused by free radicals, and gave them alcohol during pregnancy. After the mice gave birth, their exposed offspring were tested during adolescence for their ability to perform in a test of learning and memory. Among offspring exposed to alcohol, those that could not fix damaged DNA exhibited more brain damage caused by free radicals, and a decreased ability to learn for months after birth, compared to offspring from the same litter that had normal DNA repair and exhibited normal learning. Moreover, these learning deficits in the DNA repair-deficient offspring occurred at a low dose of alcohol that did not cause physical deformities. When a separate group of pregnant mice were pretreated with an agent that neutralizes or "traps" free radicals, their offspring were protected from both brain damage and the resulting behavioural problems. These results show that alcohol consumption during pregnancy can cause the formation of free radicals, which damage the brain of the developing child, resulting in learning and memory problems later in life.
Competitiondate
201209
Approvedterm2
0 yr 3 mths
Pinamesdelim
Miller, Lutfiya
Approvedterm
0 an 3 mois
Cihrcontribution2
Inst of Human Dev &Child &Yth~ $1,000~ $0~