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Aspartame brain damage in mice
See the original Hetle & Eltervaag: 2001 thesis abstract aspartame brain damage in mice: Sommewald 1995 study.
For thesis in Norwegian, mailed by regular mail, contact: Anne Værnes anne.varnes@medisin.ntnu.no "Cola light, one calorie" men hva med jhernen? Hovedfagoppgave hosten 2001 Utfort av Arnstein Eltervaag og Elisabeth Hetle Det medisinske fakultet Institutt for kliniske nevrofag Trondheim Norway 10.desember 2001 The 48-page thesis has 35 references, and includes an English abstract. Faculty and helpers listed in the Forword are: Ursula Sonnewald (with 134 items in PubMed since 1988, showing a distinguished research career in biochemical studies of neurotoxins-- one of her studies on aspartame, published 1995 with three partners, Tomm Muller, Geirmund Unsgard, and S.B. Peterson, is given in full at the end of this post, with 18 references, and obviously presents much the same laboratory technique as applied in 2001 in the thesis.), Hong Qu (female qu.hong@phys.ntnu.no), and Bente Urfjell. Obviously, this team has the experience, facilities, funding, faculty support, and motivation to study the biochemistry of aspartame toxicity in detail.
ABSTRACT Introduction: Aspartame (ASM) is a product that was originally made for diabetics, but today ASM is widely used by healthy people as an artificial sweetener in many food products. Purpose: The main goal with this research was to see whether ASM was harmful to brain cells (cerebellar granule cells). We wanted to check if the damage to the neurons is connected to the N-methyl-D-aspartate (NMDA)-receptors on these cells.
PROCEDURE Brain cells from 7 day old mice were used. They were cultured in 24 Petri well dishes, and different quantities of ASM were added. After 7 days, the cultures were analysed by two different tests: Lactate dehydrogenases (LDH) test, which gives a picture of cell death (LDH leakage to the medium in which the cells were cultured). 3-[4,5- dimethylthiazol-2yl]-2,5-diphenyltetrazolium bromid (MTT) test, which can be used to analyse mitochondrial activity in living cells. To test whether the NMDA-receptor was involved in the damage done by ASM, the receptor was blocked by (±)-2-amino-5 phosphonopentanocid (AP5).
RESULTS Our results showed damage/cell death from an added quantity of 0.06 mg/ml ASM each day for 4 days. As a comparison there is 0.24 mg/ml ASM in Cola Light. MTT- and LDH-tests showed damage to the neurons at an added quantity of 1.5 and 3.00 mg/ml ASM after 22 hours of incubation. The results also show that ASM is in part acting through the NMDA- receptor because AP5 reduced or blocked the damage to the granule cells.
CONCLUSION In light of these results, our conclusion is that in order to be on the safe side, it should be warned against use of ASM as a food additive, maybe especially in products consumed by children, because NMDA-receptors and the synapses involved also are connected to learning. ***************************************************************************************
http://www.dagbladet.no/print/?/dinside/2001/12/17/301529.html
[Photo caption] FARLIG FOR HJERNEN? Medisinstudent Elisabeth Hetle (32) har sluttet å drikke lettbrus, mens medstudent Arnstein Eltervaag (40) aldri har drukket lettbrus. I edited this into a fairly accurate English version:
[Caption for photo] DANGER FOR BRAIN? Medical student Elisabeth Hetle (32) has stopped using aspartame diet sodas, while fellow student Arnstein Eltervaag (40) has never used them.
You can also read this article at: [article on newspage] hetle@stud.ntnu.no eltervaa@stud.ntnu.no ***************************************************************************************
NTNU: Norges teknisk-naturvitenskapelige universitet:
http://www.ntnu.no/indexe.php
Faculty of Medicine:
Besøksadresse: Olav Kyrres g. ***************************************************************************************
http://www.sintef.no/units/unimed/mr/Staff/ursula.htm
http://www.ntnu.no/forskning/publikasjoner98/dmf_farmakologi ***************************************************************************************
http://www.oslo.sintef.no/annual/94/eng/14.html The MR Centre is now testing new drugs which are being developed by Yamanouchi Pharmaceuticals. The manufacturer hopes that these medicines will enable doctors to reduce brain damage in stroke patients and others who are suffering from reduced or blocked oxygen supply to the central nervous system (CNS). SINTEF UNIMED will test the new drugs by means of in vitro studies and animal tests. A lack of oxygen in the brain can lead to lasting damage since brain cells die, and because the bodily functions that are controlled by these cells are put out of operation. Damage of this sort can occur in patients who have suffered strokes, heart failure, in newborn children with paranatal injuries and people who have been rescued from drowning. However, cells whose oxygen supply is cut for a short period are capable of surviving for a day after they are damaged. In theory, this means that it ought to be possible to save many cells before the damage becomes permanent, if only we knew just what happens in the cells at this time. The photomicrograph below shows a collection of nerve cells that have built up a neural network in the petri dish. In the background we can see glial support cells (astrocytes).
BIOCHEMICAL CHANGES In collaboration with Professor Geirmund Unsgård of the University of Trondheim, Dr. Tomm Müller of Trondheim Regional Hospital and scientists from the Pharmaceutical College of Denmark, Dr. Ursula Sonnewald at the MR Centre has been studying cell cultures from mice and rats. Their studies have provided new understanding of the biochemical changes that take place during the first few hours after the oxygen supply to the brain has been cut off. Dr. Sonnewald and her partners have demonstrated differences in mechanisms of injury in the nerve cells themselves (the neurones) and the surrounding glial cells (the astrocytes) that keep the neurones alive. For this purpose she has used a spectroscopic analysis technique that utilizes nuclear magnetic resonance (NMR). In SINTEF UNIMED´s cell experiments for Yamanouchi the effects of the drugs on injured brain cells in cell cultures are studied by means of the same technique.
BRAIN IMAGES FROM LIVING ANIMALS A parallel study at SINTEF UNIMED is looking at the effects of drugs on the brains of living rats with the aid of NMR-based imaging. The special method that is being used in this part of the study was developed by Dr. Müller in the course of his doctoral studies, in collaboration with Dr. Olav Haraldseth and Dr. Richard Jones, both at SINTEF UNIMED. This method makes it possible to identify those regions of the CNS that undergo alterations when the blood supply to these animals' brains stops. The images also show the size of the areas involved. When the animals are given medication, the images can show the extent to which the injuries disappear. In this way the technique can tell us whether a given drug is capable of crossing the blood-brain barrier, as it must do if it is to have its intended effect on the central nervous system. Contact persons: Ursula Sonnewald Olav Haraldseth *************************************************************************************** (13C and 45Ca are radioactive isotopes of carbon and calcium, used to trace biochemical reactions.)
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http://www.phys.ntnu.no/instdef/grupper/biosystemer/qu.hong/ ***************************************************************************************
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