A study of GABAergic system in Scrapie-infected hamsters after striatal microinoculation of the agent

Experimental Scrapie in hamster is a simple, reproducible model of prion diseases that occur in humans and animals. Stereotaxic microinoculation (0.5 microliter) of the agent (263 K) into a specific cerebral structure (striatum) in hamster, previously developed in our group, gives the opportunity to further investigate the pathogenesis of these degenerative diseases and to more precisely define the brain areas and the groups of cells more vulnerable to the effects of the agent. In this model, early significant changes of glutamic acid decarboxylase (GAD) activity in striatum suggested a preferential alteration of the GABA system. The present study was focused on the effects of Scrapie agent directly injected into striatum on GABA neurons at the presynaptic level (GABA uptake) and at the postsynaptic level (GABAA receptors). The high-affinity [3H]GABA uptake is not changed in the Scrapie-injected striatum neither in the controlateral site and the kinetics (Km, Vmax) values are not statistically different for control and Scrapie-inoculated animals. The binding of [3H]GABA (Scatchard analysis) to cerebral membranes does not seem to be altered either at the local site of agent inoculation (striatum) neither at distance in the cerebellum: the affinity constant (Kd) to the ligand and the maximal number of receptor sites were of the same magnitude in control and Scrapie animals, but we do not have a statistical analysis. These effects are completely different of those of a neurotoxin. The present data suggest that the effects of prion agent may be very limited and very specific to some cellular mechanisms, without altering the whole cellular machinery, as recently shown in an in vitro model.(ABSTRACT TRUNCATED AT 250 WORDS)