| Summary: | 1. SUMMARY: In this thesis we reported astrocytic atrophy characterized by a reduction in the surface area and volume of GFAP-positive glial cells in the prefrontal cortex of 3xTg-AD mice - an important morphological alteration starting far before any well known histopathological hallmark of AD. This change is present in parallel with homeostatic failure suggested by the decreased expression of GS. Those alterations can have drastic effects on brain connectivity and the biochemistry of the main neurotransmitters within the brain, such as glutamate and GABA. GFAP is implicated in a variety of processes, such as cell migration and proliferation, neurite outgrowth, astrocytic glutamate transporter expression (GLAST and GLT-1) and synaptic plasticity, so that every change can shift the astrocytes' role from physiology to pathology. In the case of affected GFAP-IR astrocytes, the withdrawal of processes from neurons and synapses can lead to a severe transmission crush, due to the uncontrolled spillover of the neurotransmitter from the synaptic cleft, inadequate metabolic support and the lack of a physiological barrier between the affected synapse and other synapses in its close vicinity. This will directly disturb the reciprocal connections between the affected brain regions, inluding the important structures...
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