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 pri on diseases that occur in humans and animals. Stereotaxic microinocula tion (0.5 mu 1) of the agent (263 K) into a specific cerebral structur e (striatum) in hamster, previously developed in our group, gives the opportunity to further investigate the pathogenesis of these degenerat ive diseases and to more precisely define the brain areas and the grou ps of cells more vulnerable to the effects of the agent. In this model , early significant changes of glutamic acid decarboxylase (GAD) activ ity in striatum suggested a preferential alteration of the GABA system . The present study was focused on the effects of Scrapie agent direct ly injected into striatum on GABA neurons at the presynaptic level (GA BA uptake) and at the postsynaptic level (GABA, receptors). The high-a ffinity [H-3]GABA uptake is not changed in the Scrapie-injected striat um neither in the controlateral site and the kinetics (K-m, V-max) val ues are not statistically different for control and Scrapie-inoculated animals. The binding of [H-3]GABA (Scatchard analysis) to cerebral me mbranes does not seem to be altered either at the local site of agent inoculation (striatum) neither at distance in the cerebellum the affin ity constant (K-d) to the ligand and the maximal number of receptor si tes were of the same magnitude in control and Scrapie animals, but we do not have a statistical analysis. These effects are completely diffe rent of those of a neurotoxin. The present data suggest that the effet cs of prion agent may be very limited and very specific to some cellul ar mechanisms, without altering the whole cellular machinery, as recen tly shown in an in vitro model. However, changes in GAD activity may a lso reflect a primary change in an other neurotransmitter system that modulate the GABA system.