The relative optical density of glycogen phosphorylase and astrocytic GFAP profile in the hippocampus in a rat model of Alzheimer's disease at the pretangle stage

Haruna, Abass (2024) The relative optical density of glycogen phosphorylase and astrocytic GFAP profile in the hippocampus in a rat model of Alzheimer's disease at the pretangle stage. Masters thesis, Memorial University of Newfoundland.

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Abstract

Glycogen, a stored form of glucose, is involved in the brain's metabolism, especially in pathological conditions such as Alzheimer's Disease (AD). AD is an age-associated neurodegenerative disorder linked with cognitive deficits and increases in astrocyte reactivity (neuroinflammation). AD is preceded by the accumulation of hyperphosphorylated tau in the locus coeruleus (LC) nucleus of the brainstem as identified in Braak's pretangle stages. The current study examined relative changes in activity of glycogen phosphorylase (GP), the enzyme that breaks down glycogen for metabolic use by neurons in the hippocampus of a rat model of Braak’s LC-originated pretangle stage. An htauE14 transgene was infused in the LC of TH-Cre older rats (~χ20-month p.i) using a viral vector. Chimeric procedures for GP activity were performed with matched experimental and control brain tissue. Relative optical density (ROD) measurements of GP and astrocyte glial fibrillary acidic protein (GFAP) profile of rats in the experimental group (LC-htauE14 infused) were compared with control rats (rats without htauE14 infusion). Repeated measures analyses revealed that LC-htauE14 infusion did not alter the GP levels (aGP, tGP, and ratio) and the astrocyte GFAP expression in the hippocampus of these rats at the pretangle stage of AD. There were no sex-dependent alterations detected. However, various subregions within the hippocampal DG, CA3 and CA1 showed different levels of GP activity and GFAP profiles regardless of sex and condition. These findings indicate that GP and GFAP ROD are not altered at the pretangle stage of AD, suggesting the potential existence of compensatory mechanisms in addressing energy demands at the early phases of AD.

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