Διατμηματικό / Διϊδρυτικό ΠΜΣ Μοριακή Ιατρική
Library of the School of Health Sciences

2015-09-25

2015

Μαυροειδή Παναγιώτα

Καθηγητής Ευθυμιόπουλος Σπυρίδων

Μελέτη της επίδρασης της στέρησης γλυκόζης και οξυγόνου σε νευροπροστατευτικούς μηχανισμούς του εγκεφάλου.

Greek

Study of the effect of glucose and oxygen deprivation on neuroprotective mechanisms.

Background: Alzheimer’s Disease (AD) is the most common form of dementia, with
two major neuropathological features, including intracellular neurofibrillary
tangles (NFTs) consisting of hyper-phosphorylated tau, and extracellular
amyloid plaques. Hyper-phosphorylation of tau decreases its affinity for the
microtubules, resulting in accumulation of the protein in the axons and
disruption of the normal neuronal function. Cerebral blood hypoperfusion and
subsequent elimination of oxygen and glucose supply to the brain are believed
to be involved in the development of sporadic AD. Based on these data, we
investigated the effects of glucose and oxygen deprivation on tau
phosphorylation and depolarization-induced signaling.
Methods: Perfusion of acute brain slices from C57BL/6 mice with artificial
cerebrospinal fluid supplemented with various oxygen and glucose
concentrations. Total protein extracts were analyzed by SDS-PAGE.
Results: Hypoxia reduced the phosphorylation of tau in all the examined
residues. This effect was more potent when oxygen deprivation was combined with
low levels of glucose in the perfusion medium. However, glucose deprivation,
alone, did not affect phospho-tau levels. Finally, hypoxia, but not
hypoglycemia, resulted in complete attenuation of depolarization-induced
neuroprotective signaling.
Conclusions: The hypophosphorylation of tau under hypoxic conditions could be
attributed to an extensive down-regulation of energy metabolism, as a temporary
neuroprotective mechanism against limited oxygen supply. Although these
particular stress conditions failed to induce pathological phosphorylation of
tau protein, they may exert their neurotoxic effects through impairment of
depolarization-induced signaling, which is vital for normal neuronal function
and survival.

Glucose, Oxygen, Neuroprotection, Alzheimer's disease, Depolarization

Yes

81-82

Yes

237

103

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https://pergamos.lib.uoa.gr/uoa/dl/object/1312464