Alzheimer's disease (AD) is a neurodegenerative central nervous system (CNS) disorder that represents one of the most common causes of death in Western countries. With the continuing exponential increase in the aged population, 34 million people world-wide will suffer from AD by 2025. Because the current therapeutic strategies aim to relieve only the symptoms of AD, it is necessary to find new therapeutical targets that have a potential impact on the development of the disease. In this respect the glutamate transporters are potential candidates for innovative pharmacological interventions.
AD is characterized clinically by a progressive cognitive impairment and pathophysiologically by regional neuronal loss. This loss may result from an excitotoxic process in which glutamate transporters may play an important role. Amyloid precursor protein (APP23) transgenic mice, a unique AD model, carry the Swedish double mutation, known to cause early-onset familial AD in humans.
Until now, not much is known with respect to the glutamate transporters in AD. These transporters regulate excitatory neurotransmission and prevent glutamate-mediated excitotoxicity in the CNS. Three vesicular glutamate transporters (vGlut1-3) have been identified. They upload glutamate into synaptic vesicles and share similar pharmacologic characteristics. Glutamate transporter-1 (Glt-1) and glutamate aspartate transporter (Glast), the 2 glial high-affinity Na+/K+-dependent glutamate transporters, are the major plasma membrane glutamate uptake proteins. They are responsible for removing extracellular glutamate in the CNS.
In the present study, the possible changes in expression level of vGlut1-3, Glt-1 and Glast are examined by means of Western blotting and immunohistochemistry in 8 month old wild type (WT) and APP23 mice using a double blind methodology. The AD sensitive regions (hippocampus, cortex, striatum and hypothalamus) of both types of mice are compared. In a preliminary phase of this study, we searched for an appropriate control for the Western blotting. We compared the house-keeping genes glyceraldehyde-3-phosphate dehydrogenase (GAPDH), tubulin and synapsin IIa. Since no changes could be detected in the expression levels of GAPDH and tubulin, between WT and APP23 mice, they are considered as being suitable house-keeping genes in our experimental set-up. Ongoing experiments investigate the possible changes of the vGluts, Glt-1 and Glast. The results will be reported and discussed at the meeting.
Original languageEnglish
Title of host publicationSpa, Belgisch Genootschap voor Farmaceutische Wetenschappen, dertiende forum
Publication statusPublished - 12 Oct 2007

    Research areas

  • glutamate transoprters, APP23 model

ID: 1751454