Excitotoxic effects of non-NMDA receptor agonists in organotypic corticostriatal slice cultures
| Autor: | Jan Bert Gramsbergen, Bjarke Ebert, Bjarne Winther Kristensen, Jens Zimmer, Birthe Jakobsen, Jens Noraberg |
|---|---|
| Rok vydání: | 1999 |
| Předmět: |
medicine.medical_specialty
Kainic acid Glutamate decarboxylase Neurotoxins Kainate receptor Neocortex AMPA receptor Striatum Biology gamma-Aminobutyric acid chemistry.chemical_compound Organ Culture Techniques Internal medicine Quinoxalines medicine Excitatory Amino Acid Agonists Animals Rats Wistar Molecular Biology alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid gamma-Aminobutyric Acid Cerebral Cortex Kainic Acid L-Lactate Dehydrogenase Glutamate Decarboxylase General Neuroscience Glutamate receptor Corpus Striatum Rats Endocrinology Neuroprotective Agents nervous system chemistry Biochemistry Animals Newborn NBQX Neurology (clinical) Excitatory Amino Acid Antagonists Developmental Biology medicine.drug |
| Zdroj: | Kristensen, B W, Noraberg, J, Jakobsen, B, Gramsbergen, J B, Ebert, B & Zimmer, J 1999, ' Excitotoxic effects of non-NMDA receptor agonists in organotypic corticostriatal slice cultures ', Brain Research, vol. 841, no. 1-2, pp. 143-159 . https://doi.org/10.1016/S0006-8993(99)01833-8 |
| ISSN: | 0006-8993 |
| DOI: | 10.1016/S0006-8993(99)01833-8 |
| Popis: | Udgivelsesdato: 1999-Sep-11 The excitotoxic effects of the glutamate receptor agonists kainic acid (KA) and 2-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) and the corresponding neuroprotective effects of the AMPA/KA receptor antagonist 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(F)quinoxaline (NBQX) were examined in corticostriatal slice cultures. The purpose was to examine the feasibility of these cultures for excitotoxic studies, and to demonstrate possible differential excitotoxic effects of KA and AMPA on striatal and cortical neurons. Slices of dorsolateral striatum with overlying neocortex were obtained from neonatal rats and grown on semiporous membranes in serum-free medium for 3-4 weeks before exposure to KA or AMPA for 48 h. The uptake by injured cells of the fluorescent dye propidium iodide (PI) added to the culture medium was used as a quantifiable measure for neuronal degeneration and compared with efflux of the cytosolic enzyme lactate dehydrogenase (LDH) into the culture medium and loss of glutamic acid decarboxylase (GAD) activity in the tissue. Histological sections were also stained by the fluorescent dye Fluoro-Jade (FJ), for degenerating neurons and by immunocytochemical staining for gamma-aminobutyric acid (GABA). Digitized images showed a dose (0-24 microM KA, 0-6 microM AMPA) and time (0-48 h) dependent increase in PI uptake in both striatum and cortex. In other cultures exposed to KA (24 microM) or AMPA (6 microM) together with NBQX (0.1-9 microM), NBQX was found to exert a differential neuroprotective effect on striatum and cortex at low doses. NBQX was thus more protective against KA in the cortex than in the striatum, while the opposite was seen in relation to AMPA. Regarding neurodegenerative markers, PI uptake was significantly correlated with (1) LDH release into the culture medium, (2) optical density of Fluoro-Jade staining, (3) loss of GAD-activity in tissue homogenates, and (4) loss of GABA-immunostained neurons. We conclude that both differences between compounds (AMPA vs. KA) and brain areas (striatum vs. cortex) can be demonstrated in corticostriatal slice cultures, which in conjunction with an established set of markers for neuronal cell damage appears to be a feasible model for studies of the neurotoxic and neuroprotective effects of glutamate receptor agonists and antagonists. |
| Databáze: | OpenAIRE |
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