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Elevated L-Lactate Drives Major Cellular Pathologies Associated with Neurodegeneration
Başlık:
Elevated L-Lactate Drives Major Cellular Pathologies Associated with Neurodegeneration
Yazar:
Behnke, Jessica E., author.
ISBN:
9780355979510
Yazar Ek Girişi:
Fiziksel Tanımlama:
1 electronic resource (86 pages)
Genel Not:
Source: Masters Abstracts International, Volume: 57-06M(E).
Advisors: Qing-Hui Chen; Andrew D. Chapp Committee members: Zhiying Shan.
Özet:
Within the past few decades, lactate research has expanded from initial findings deeming lactate as a dead-end metabolic product to recognition of lactate's role as a potential energy substrate in the CNS. Due to the tight relationship between lactate and energy metabolism, interest in the scientific community has been mounting around associations among metabolic dysregulation, elevated lactate and neurodegenerative states such as Alzheimer's, Parkinson's, amyotrophic lateral sclerosis, ischemia/reperfusion (AD, PD, ALS, I/R injuries), and physiological aging, however underlying cellular mechanisms and/or facilitators for neuronal degeneration pathologies still remain unknown. Here, we tested several hypotheses that implicate L-lactate to various neurodegenerative mechanisms: increases in cytosolic calcium, increases in cytosolic reactive oxygen species (ROS), increases in intracellular acidification, and subsequently, increases in cellular death in primary neuronal cultures and dopaminergic-like NGF-derived PC12 cells. Treatment of cells with a pathologic concentration of L-lactate (4 mM) induced significant increases in cytosolic calcium, cytosolic ROS, and intracellular acidification measured in real time with fluorescent markers and quantified using ImageJ software. Furthermore, treatment with L-lactate (4 mM) induced significant increases in cell death, measured in real time and using flow cytometry in support. We conclude that L-lactate increases cellular events commonly observed in cells undergoing degeneration, providing support for the implications of lactate in neurodegenerative disorders.
Notlar:
School code: 0129
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Yer Numarası | Demirbaş Numarası | Shelf Location | Lokasyon / Statüsü / İade Tarihi |
---|---|---|---|
XX(690672.1) | 690672-1001 | Proquest E-Tez Koleksiyonu | Arıyor... |
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