000009740 001__ 9740
000009740 005__ 20240124114329.0
000009740 0247_ $$2DOI$$a10.6083/mg74qm961
000009740 037__ $$aETD
000009740 245__ $$aExploring DNA double strand breaks as an underlying mechanism of learning and the influence of apolipoprotein E
000009740 260__ $$bOregon Health and Science University
000009740 269__ $$a2022
000009740 336__ $$aDissertation
000009740 502__ $$bPh.D.
000009740 520__ $$aDNA double strand breaks (DSBs) lead to apoptosis or tumorigenesis. The complexity of their repair has led to DSBs being classified as the most harmful type of DNA damage. In a sudden shift, a novel role for DSBs in immediate early gene (IEG) expression, learning, and memory has been suggested. Inducing neuronal activity in vitro and learning events in vivo lead to increases in DSBs and upregulation of IEGs. Additionally, inhibiting DSB repair and increasing DSBs impair long-term memory and alter IEG expression. DNA damage increases and DNA repair decreases with aging; post-mortem tissue from patients diagnosed with mild cognitive impairment or Alzheimer?s disease (AD) in life show increases in DSBs.
Altogether, this dissertation adds to the evidence that DSBs have an adaptive function in the brain, and that minor alterations in typical DSB formation and repair can alter IEGs, learning, and memory.
000009740 542__ $$fIn copyright - single owner
000009740 650__ $$aMemory$$022012
000009740 650__ $$aAging$$014358
000009740 650__ $$aLearning$$021358
000009740 650__ $$aApolipoproteins E$$014992
000009740 6531_ $$adouble-stranded dna breaks
000009740 6531_ $$aimmediate early gene
000009740 691__ $$aSchool of Medicine$$041369
000009740 692__ $$aDepartment of Behavioral Neuroscience$$041394
000009740 7001_ $$aBoutros, Sydney W.
000009740 8564_ $$96424c1c7-f3b1-4783-b6f6-1ebca7d25862$$s19714288$$uhttps://digitalcollections.ohsu.edu/record/9740/files/Boutros.Sydney.2022.pdf
000009740 905__ $$a/rest/prod/mg/74/qm/96/mg74qm961
000009740 909CO $$ooai:digitalcollections.ohsu.edu:9740$$pstudent-work
000009740 980__ $$aTheses and Dissertations