Effects of Hyperglycemia on the Morphology and Mitochondrial Activity in Cultured Embryonic Cortical Neurons
Date Issued
2015
Date
2015
Author(s)
Chiang, Shu-Jen
Abstract
Hyperglycemia is a key pathogenetic feature of diabetes mellitus and diabetic complications. There is considerable evidence that hyperglycemia is not only closely related to diseases such as senile cataracts and arteriosclerosis, but is also implicated in neurodegenerative diseases Alzheimer’s disease (AD), Parkinson’s disease (PD), and amyotrophic lateral sclerosis (ALS). In this study, we are interested in the defects in neuronal morphology and mitochondrial activity caused by high glucose insult as a first step toward understanding the events that underlie the development of neurodegenerative diseases. To characterize the effects of high glucose on neurons, this work is divided into two parts, the first part focuses on the morphology of neural dendrites and spine density on the basis of three dimensional (3D) images from confocal microscope; the second part studies the physiological function of mitochondria using TMRM fluorescence and MTT assay. Our findings show that high glucose is associated with drawback in branching point initiation and dendrite extension; in addition, spine outgrowth is abnormal. Regarding the mitochondria, the membrane potential across the inner membrane is perturbed as in apoptotic stress but no immediate cell death is observed. Taken together, these phenomena may play important roles in the pathogenesis of maternal hyperglycemia-induced CNS malformations. The result may also be the underlying mechanisms that cause certain aged people more vulnerable to inflict neurodegenerative diseases. In the future, in vivo study on STZ-induced diabetic mother and its embryo will be carried out for comparative study, with further investigation on the effects of hyperglycemia upon mitochondrial deoxyribonucleic acid (mtDNA).
Subjects
Hyperglycemia
diabetes mellitus
senile cataracts
arteriosclerosis
Alzheimer’s disease
Parkinson’s disease
amyotrophic lateral sclerosis
neurodegenerative disease
confocal microscope
dendrite
spine
TMRM
MTT assay
mitochondria
mitochondrial deoxyribonucleic acid
SDGs
Type
thesis
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