Excitotoxicity-induced expression of amyloid precursor protein (beta-APP) in the hippocampus and cortex of rat brain. an electron-microscopy and biochemical study.
After stereotaxic microinjection of N-methyl-D-aspartate (NMDA) or alpha-amino-3-hydroxy-5-methyl isoxazole-4-propionic acid (AMPA) to CA1 of rat hippocampus, the animals were sacrificed: 0 h, 2 h, 12 h, 24 h and 3 days after the insult. Other groups of animals before microinjection of the excitotoxins received intraperitoneal injection of dizocilpine (MK-801). Expression of beta-APP was assessed by immunohistochemical and immunobiochemical methods, and the results were correlated with changes in tissue ultrastructure observed in the electron microscopy. The results of the immunochemical analyses study demonstrated that application of NMDA and AMPA resulted in the increase of the expression of beta-APP in the CA1 of hippocampus and to a less extent in the cortex. Pretreatment with MK-801 strongly suppressed this effect. Beta-amyloid release was not detected. Morphological and cytochemical study revealed that NMDA injection induced massive damage of hippocampal and cortical neurones, associated with mitochondrial calcium sequestration and unusual accumulation of neurofilaments. Ultrastructural changes after AMPA application were limited to the brain cortex. These data indicate that although excitotoxic insult induces hyperexpression of beta3-APP, there is no relation between this effect and neurodegeneration, and excitotoxicity does not induce amyloidogenic processing of beta-APP.
Gordon-Krajcer
W
W
Department of Neurochemistry, Medical Research Centre, Polish Academy of Sciences, Warszawa.
Gajkowska
B
B
D016564:Amyloid beta-Protein Precursor / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure*; D016291:Dizocilpine Maleate / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure*; D007150:Immunohistochemistry; D008297:Male; D016202:N-Methylaspartate / Q000009:adverse effects* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018091:Receptors, AMPA / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D013238:Stereotaxic Techniques; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000009:adverse effects* / Q000378:metabolism
D016564:Amyloid beta-Protein Precursor; D018696:Neuroprotective Agents; D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; D016202:N-Methylaspartate; D016291:Dizocilpine Maleate; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid