NR AJTX
AU Quinn,M.R.; Kim,Y.S.; Lossinsky,A.S.; Carp,R.I.
TI Influence of stereotaxically injected scrapie on neurotransmitter systems of mouse cerebellum
QU Brain Research 1988 Apr 5; 445(2): 297-302
PT journal article
AB The 22L strain of scrapie was injected stereotaxically into the cerebellum of C57BL/6J mice to determine its effect on several cerebellar neurotransmitter systems during the early clinical stages of the disease. In this model vacuolar lesions are restricted to the cerebellum with no evidence of vacuolization in other brain regions. Although vacuolar lesions develop throughout all cell layers of the cerebellum, they are most severe in the granule cell layer. Modest but significant (P less than 0.01) reductions in cerebellar weight, glutamate decarboxylase activity, and in the affinity of the N6-[adenine-2,8-3H]cyclohexyladenosine binding sites, were observed in scrapie affected mice. The densities of the high- and low-affinity adenosine receptors were unaffected. Adenosine receptors in the cerebellum are highly localized to the axon terminals of the glutamatergic, GABA receptive granule cells. GABA, benzodiazepine, glutamate, and muscarinic cholinergic receptors were not significantly altered. In addition, the high-affinity uptake of glutamate, and the activity of choline acetyltransferase were not significantly changed. GABA high-affinity uptake was slightly increased. Even though the granule cell layer of the cerebellum had undergone severe vacuolation, only modest neurotransmitter changes were apparent. Although these results suggest a tenuous relationship between scrapie pathology and the integrity of neurotransmitter systems, it is possible that compensatory neurochemical changes in uncompromised neuronal populations may have masked potentially specific neurotransmitter effects.
IN Scrapieagens vom Stamm 22L wurde C57BL/6J-Mäusen ins Kleinhirn injiziert. Die Mäuse entwickelten nur im Kleinhirn die krankheitstypischen Vakuolen. Die Vakuolen entstanden in allen Schichten des Kleinhirns, am stärksten jedoch in der granulären Zellschicht. Bei den infizierten Mäusen wurden leichte, aber signifikante Reduktionen der Kleinhirnmasse, der Glutamatdecarboxylaseaktivität und der Affinität der Bindungsstellen für N6-[Adenin-2,8-3H]cyclohexyladenosin festgestellt. Die Dichte der Adenosinrezeptoren mit hoher bzw. niedriger Affinität blieb unverändert. Auch bei den Rezeptoren für GABA, Benzodiazepin, Glutaminsäure und den muscarinischen cholinergen Rezeptoren wurden keine signifikanten Veränderungen festgestellt. Die hochaffine Aufnahme von Glutaminsäure und die Aktivität der Cholin acetyltransferase waren nicht signifikant verändert. Nur die hochaffine GABA-Aufnahme war leicht erhöht.
MH Animal; Cerebellum/*metabolism; Choline/metabolism; Female; Glutamates/metabolism; Glutamic Acid; Kinetics; Mice; Mice, Inbred C57BL; Neurotransmitters/*metabolism; Receptors, Cell Surface/*metabolism; Reference Values; Scrapie/*metabolism; Stereotaxic Techniques; Support, U.S. Gov't, P.H.S.
AD New York State Office of Mental Retardation and Developmental Disabilities, Staten Island 10314.
SP englisch
PO Niederlande