Fine structural localization of glutamine synthetase in astrocytes of rat brain.

Light microscopy immunohistochemical techniques were used to examine the distribution of glutamine synthetase in rat brain. Glutamine synthetase was found to be localized in the glial cells. Neuronal cell bodies, endothelial cells, and choroid epithelium contained no enzyme. The findings indicate that glia have a crucial role in glutamic acid, gamma-aminobutyric acid, and ammonia metabolism in brain.

https://science.sciencemag.org/content/sci/195/4284/1356.full.pdf

Glutamine synthetase: glial localization in brain.

Metabolism of the neurotoxic tertiary amine, MPTP, by brain monoamine oxidase.

Electrographic, clinical and pathological alterations following systemic administration of kainic acid, bicuculline or pentetrazole: metabolic mapping using the deoxyglucose method with special reference to the pathology of epilepsy

Isolation of synaptic plasma membrane from brain by combined flotation-sedimentation density gradient centrifugation.

Ultrastructural and enzymic studies of cholinergic and non-cholinergic synaptic membranes isolated from brain cortex.

THE FINDING that dogs underwent seizures after ingestion of flour from NC13-treated wheat (MELLANBY, 1946) led to the isolation of methionine sulphoximine (MSO) as the toxic convulsant factor (BEKTLEY, MCDEXMOTT, MORAN, PACE and WHITEHEAD, 1950; MISANI and REINER, 1950; REINER, MISANI and WEISS, 1950). Because of the similarity of the convulsions to those of human epilepsy this agent has been the object of numerous physiological and neurochemical studies (see WOLFE and ELLIOT, 1962). Several investigations pointed toward a possible causal relationship between MSO and a disequilibrium in glutamine-glutamic acid metabolism. PETERS and TOWER (1959) found a marked inhibition of glutamine synthesis in brain slices of MSO-treated cats, and a relationship between amidation of glutamic acid in brain and seizures was also postulated in rats after MSO or acoustic epileptogenic stimulation by KOLOUSEK, HORAK and JIRACEK (1959). SELLINGER and WEILER (1963) reported that in vitro MSO competitively inhibits glutamine synthetase (GS), and more recently LAMAR and SELLINGER (1965) found that in vivo the drug inhibits GS irreversibly. In this last paper some preliminary observations on the subcellular distribution of labelled MSO were made and evidence was reported that it is preferentially bound to the microsomal fraction isolated from an homogenate in water, which is particularly rich in GS (DE BALBIAN VERSTER, SELLINGER and HARKIN, 1965). Recently SALGANICOFF and DE ROBERTIS (1965) analysed the subcellular distribution of GS and other enzymes related to the metabolism of glutamate, glutamine and GABA. The fractionation procedure, carried out in sucrose solutions under standard conditions and with electron microscopic control, enabled them to follow the localization of certain enzymes in well defined subcellular fractions of the CNS such as mitochondria, myelin, and particularly nerve endings, synaptic vesicles and membranes. In agreement with the results of WAELSCH (1959) and SELLINGER and DE BALBIAN VERSTER (1962), GS was found to be concentrated in the microsomal fraction.

Martha Alberici

Papers

Ultrastructural and enzymic studies of cholinergic and non-cholinergic synaptic membranes isolated from brain cortex.

Nerve endings in methionine sulphoximine convulsant rats, a neurochemical and ultrastructural study*

Glutamic acid decarboxylase inhibition and ultrastructural changes by the convulsant drug allylglycine.

Astroglial swelling and phosphohydrolases in cerebral cortex of metrazol convulsant rats

Isolation and properties of isolated nerve ending membranes and junctional complexes