AJOU Central Library Repository: LDHB 유전자 삭제에 의한 허혈성 신경세포 사멸 감소

Graduate School of Ajou University Department of Biomedical Sciences 3. Theses(Master)

LDHB 유전자 삭제에 의한 허혈성 신경세포 사멸 감소

Alternative Abstract: Although brain occupies only 2% of body weight, it consumes approximately 25% of the body's total energy and neuronal activity comprise 80% of brain energy requirement. Thus, neurons are particularly vulnerable to situations where energy source is lacking, such as ischemia. It is well known that lactate constitutes important energy source of brain energy metabolism. How lactate supports the survival of neuronal cells is well explained by astrocyte-to-neuron lactate-shuttle hypothesis. This study focuses the role of lactate dehydrogenase B (LDHB) in neuronal cell homeostasis, which is the major enzyme in lactate-shuttle theory. For this purpose, LDHB knockout mice were generated. Both in vivo and in vitro assays show that ischemic neuronal cell death is attenuated by LDHB loss. In vivo ischemic condition, PcomA (posterior communicating artery) size of LDHB KO mice is bigger than that of WT mice. These results suggest that increased PcomA size in LDHB KO mice may be contribute to neuronal cell survival. The increase of PcomA size in LDHB KO brain is further supported by the fact that mRNA level of VEGFA (vascular endothelial growth factor A) is highly increased in LDHB KO neuronal primary cells after treatment with cobalt chloride (CoCl2), which is hypoxia mimetic agent. Taken together, loss of LDHB might cause metabolic changes and that lead to decrease the ischemic neuronal cell death by increasing PcomA size and upregulating VEGFA level.

Appears in Collections:: Graduate School of Ajou University > Department of Biomedical Sciences > 3. Theses(Master)

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