Poddar 2016 Abstract IOC116
|Poddar J, Banerjee A, Mukherjee A, Chakrabarti S (2016) Effects of glucose hypometabolism on mitochondrial functions in rat brain and in SHSY5Y cells in culture. Mitochondr Physiol Network 21.11|
Link: Mitochondr Physiol Network 21.11
The pathogenic mechanisms of sporadic Alzheimer's disease (AD), the commonest cause of pathological dementia in the elderly people, are unknown, but a proteotoxic mechanism through the abnormal accumulation, oligomerization and aggregation of amyloid beta peptide (Aβ42 and Aβ40) is considered to be the driving force of the disease (Amyloid cascade hypothesis). In contrast, other studies have indicated a strong metabolic component in AD pathogenesis. In particular, diminished cerebral glucose uptake and metabolism is a cardinal feature of AD pathogenesis that is seen in all stages of the disease and well correlated with the extent of cognitive decline. In order to elucidate further the effects of glucose hypometabolism on mitochondrial functions and neuronal viability, we subjected SHSY5Y cells in culture to glucose hypometabolic stress by exposure to 2-D-Deoxyglucose or 2-DG (1-4 mM) for 48 h. Under such experimental conditions we observed dose-dependent, non-apoptotic cell death with oxidative stress and alterations in mitochondrial membrane potential in SHSY5Y cells in culture. In order to examine the effects of 2-DG in animals, young Wistar rats were given intraperitoneal injections of the compound at a dose of 300 mg /kg for 10 days and brain mitochondrial functions were assessed in terms of oxygen consumption rate, transmembrane potential, ATP synthesis and respiratory chain complex activities. However, no significant difference was observed in these parameters between control and experimental animals. The effects of 2-DG on brain mitochondrial functions, amyloid homeostasis and possible neurodegeneration will now be analyzed after intracerebroventricular administration of the compound in rats.
• O2k-Network Lab: IN Haldia Chakrabarti S
Labels: MiParea: Pharmacology;toxicology Pathology: Alzheimer's
Organism: Rat Tissue;cell: Nervous system, Other cell lines
1-Dept Biochem, Inst Post-graduate Med Education & Research, Kolkata; 2-ICARE Inst Med Sci & Research, Haldia, West Bengal; 3-St. Xavier’s College, Taltala, Kolkata, West Bengal; India. - [email protected]