NR ADQW

AU Durand-Gorde,J.M.; Bert,J.; Nieoullon,A.

TI Changes in tyrosine hydroxylase, glutamic acid decarboxylase and choline acetyltransferase after local microinoculation of scrapie agent into the nigrostriatal system of the golden hamster

QU Brain Research 1985 Aug 26; 341(2): 243-51

PT journal article

AB A microinjection of a homogenate of scrapie agent-infected brain (strain 263 K) into the nigrostriatal system in the golden hamster is followed by the progressive development of the disease which terminates by the death of animals around the 4th month postinoculation. These intracerebral inoculations induce more rapid changes in neuronal activity which can be revealed by the assessment of the specific synthesizing enzymes of neurotransmitter systems. The microinoculation of a homogenate of an infected brain unilaterally into the substantia nigra (SN) provokes a decrease in tyrosine hydroxylase (TH), the synthesizing enzyme for dopamine in the dopaminergic neurones, in the striatum ipsilateral to the injected SN. This biochemical response, specifically induced by the active pathogen, is detectable as soon as the 5th day postinoculation and is detectable towards the 80th day. A return of TH levels to control values is detected after this period. At the end of the incubation period and towards the death of the animals, TH is not different from control TH measured from intact animals. The decrease in TH is concomitant with an increase in striatal glutamic acid decarboxylase (GAD), the synthesizing enzyme for gamma-aminobutyric acid (GABA), measured 20 days postinoculation with no change in choline acetyltransferase (ChAT), the synthesizing enzyme for acetylcholine. Studies of the biochemical responses associated locally to the scrapie agent inoculation have been performed at the striatal level. The intrastriatal administration of the infective agent induces 20 days postinoculation an increase in GAD with no change in TH and ChAT. Ninety days postinoculation, a decrease in GAD was detected associated with an increase in TH with no change in ChAT.(ABSTRACT TRUNCATED AT 250 WORDS)

IN Goldhamster starben rund 4 Monate nach einer Microinjektion von mit dem Scrapiestamm 263 K infiziertem Gehirnmaterial in die Substantia nigra (melaninhaltige Nervenzellen enthaltender Kern zwischen Pedunculus cerebri (Pars ventralis) und Tegmentum des Mittelhirns). Bereits 5 Tage und bis zum 80. Tag nach der Injektion direkt in die Substantia nigra nur einer Gehirnhälfte war die Konzentration der Tyrosinhydroxylase (das in den dopaminergen Neuronen Dopamin synthetisierende Enzym) rund um die Injektionsstelle reduziert. Danach normalisierte sich die Konzentration der Tyrosinhydroxylase wieder blieb während der gesamten Krankheitsphase normal. Räumlich und zeitlich korrelierte die Reduktion der Konzentration der Tyrosinhydroxylase mit einer Zunahme der Glutaminsäuredecarboxylase, welche die gamma-Aminobuttersäure synthetisiert. Bei der Acetylcholin synthetisierenden Cholinacetyltransferase wurde hingegen keine Veränderung festgestellt.

MH Animal; Choline O-Acetyltransferase/*metabolism; Comparative Study; Corpus Striatum/drug effects/*enzymology/microbiology; Female; Glutamate Decarboxylase/*metabolism; Hamsters; Hydroxydopamines/pharmacology; Kainic Acid/pharmacology; Male; Mesocricetus; Oxidopamine; *Prions; Substantia Nigra/drug effects/*enzymology/microbiology; Support, Non-U.S. Gov't; Tyrosine 3-Monooxygenase/*metabolism

SP englisch

PO Niederlande

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