Informa Poster Prize Winner P48 - Evaluation of Mitochondrial Function in the CNS of Rodent Models of Alzheimer's Disease - High Resolution Respirometry Applied to Acute Hippocampal Slices

Abstract

Alzheimer's disease (AD) is a multifactorial disease characterized by extracellular deposits of amyloid plaques and intracellular neurofibrillary tangles. These hallmark alterations are preceded by synaptic deterioration, changes in neuromolecular plasticity phenomena, mitochondrial dysfunction, increase in oxidative damage to cellular constituents and decreased energy metabolism. The hippocampus is a structure of the temporal medial lobe implicated in specific forms of memory processes. It is also one of the first and most affected regions of the CNS in AD.Here we present a novel approach to the study if mitochondrial function/disfunction in 2 rodent models of AD: an acute rat model obtained by intracerebroventricular injection of the toxin streptozotocin (STZ) and a progressive triple transgenic mouse model (3TgAD) harboring PS1M146V, APPSwe, and tauP301L transgenes. Mitochondrial dysfunction has classically been assessed in such models by isolating mitochondria, synaptossoms or working with cell cultures. Anyone of these approaches destroys the intricate intercellular connectivity and cytoarchitecture of neuronal tissue. We used acute hippocampal slices obtained from the 2 models of AD and evaluated changes in mitochondrial function as a function of disease and/or age. Mitochondrial stress test were performed on the high resolution respirometry (Oroboros 2K Oxymeter).Upon analysis of oxygen consumption rates (OCR) we observed significant decreases in basal OCR, maximal respiratory capacity, ATP turnover and a tendency for decrease in sparing capacity in the STZ rat model compared to shame injected animals. Regarding the 3TgAD model we observed an age-dependent decrease in all parameters evaluated in the mitochondrial stress test, in both 3TgAD and NTg animals. However, although a tendency towards decreased OCR was observed when comparing 3TgAD and age-matched NTg animals, no statistically significant difference was observed.