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Biomedical subjects

F Fonnum

Publications and source records attributed to F Fonnum.

224 records · Page 13Linked to original sources
PubMed1966

A radiochemical method for the estimation of choline acetyltransferase.

1. A radiochemical method for the estimation of choline acetyltransferase (choline acetylase) has been devised which involves the formation of labelled acetylcholine from labelled acetate. 2. [1-(14)C]Acetate and coenzyme A are pre-incubated in the presence of non-rate-limiting concentrations of acetyl-coenzyme A synthetase to give [1-(14)C]acetyl-coenzyme A, which then reacts with choline in the presence of the acetyltransferase to give [(14)C]acetylcholine. 3. Any [(14)C]-acetyl-coenzyme A remaining at the end of the reaction is destroyed by the addition of excess of hydroxylamine, and [(14)C]acetylcholine is freed from other labelled compounds by precipitation with sodium tetraphenylborate (Kalignost). 4. The washed precipitate is dissolved in acetonitrile-benzyl alcohol and estimated by scintillation counting. 5. Advantages over other methods are discussed.

Animals↗
PubMedDate not supplied

Persistent changes in behaviour and brain serotonin during ageing in rats subjected to infant nasal virus infection.

Suckling rats were infected intranasally with the temperature-sensitive mutant G41 strain of vesicular stomatitis virus. The rats survived but demonstrated lifelong learning deficits in the Morris maze and impaired exploratory behaviour in the open field test. When examined at 18 months of age they had a severe loss of neurons in the medial and dorsal raphe nuclei in the brain stem and reduced levels of serotonin and its metabolite 5-hydroxyindole acetic acid in the cerebral neocortex and hippocampus. The levels of noradrenaline, dopamine, homovanillic acid, 3,4-dihydroxyphenylacetic acid, choline acetyltransferase and glutamate decarboxylase were largely unaffected. The permanent disturbance in brain serotonin metabolism did not cause any histological changes in the cerebral cortex. Thus there were no neurofibrillary tangles or amyloid plaques as has been reported as a late effect of chemically induced lesion to the cholinergic system in the rat brain. It is concluded that the brain serotonergic system is especially vulnerable to an episode of virus attack along olfactory pathways and that the neurochemical and behavioural alterations caused by such an episode persist during a major part of the animal's life span.

Aging↗
PubMedDate not supplied

Teratogenic effects of trichlorfon (Metrifonate) on the guinea-pig brain. Determination of the effective dose and the sensitive period.

The conditions (sensitive period and doses) for producing hypoplasia in guinea-pig offspring after treatment of pregnant guinea-pigs with the organophosphorous agent trichlorfon (metrifonate, 0,0-dimethyl 2,2,2-trichloro-1-hydroxyethylphosphonate) were examined. The results showed that the minimal dose required was 100 mg/kg on three consecutive days. For the cerebellum the most sensitive period was 42-44 day of gestation, for cortex the most vulnerable period was gestational days 48-50. The doses could be given either per os or subcutaneously. Almost all regions of the brain were reduced in weight. Cerebellum was the most vulnerable region, but also the medulla and hypothalamus were greatly reduced in weight. The mechanism behind the teratogenic effect is not known, but alkylation of DNA or an effect on its repair mechanism are possible effects.

Animals↗
PubMedDate not supplied

Brain hypoplasia caused by exposure to trichlorfon and dichlorvos during development can be ascribed to DNA alkylation damage and inhibition of DNA alkyltransferase repair.

Treatment of pregnant guinea pigs with trichlorfon causes cerebellar hypoplasia in offspring. The most sensitive period for treatment is days 42-47 of gestation, which coincides with the rapid brain growth spurt and with the development of cerebellar granule cells. When rat granule cells were exposed in vitro to trichlorfon and dichlorvos for 24 hours they died, whereas trichloroethanol had no effect. When the cells were exposed to trichlorfon and dichlorvos for 3 hours, only dichlorvos was lethal indicating that the metabolite dichlorvos was more potent than trichlorfon itself. Cultured cerebellar granule cells were also found to be quite sensitive to other DNA-alkylating agents such as methylazoxymethanol and methylmethane sulphonate and to O6-benzylguanine; a potent and specific inhibitor of the DNA alkyltransferase involved in the repair of DNA alkylation damage. The organophosphorous compounds were also found to cause inhibition of the alkyltransferase and the lethal effects of the tested compounds on granule cell culture correlated well with the potency of inhibition. In a bacterial test system for monitoring alkylation effects on the DNA, dichlorvos was demonstrated to have a strong DNA alkylation effect. These results suggest that alkylation of DNA and inhibition of its repair can contribute to the brain hypoplasia observed after exposure to trichlorfon and dichlorvos during brain development.

Alkyl and Aryl Transferases↗