Effect of Bacterial Flora and Mouse Genotype (Euthymic or Athymic) on Scrapie Pathogenesis

Abstract

Euthymic and athymic female BALB/c mice, reared under either germfree or defined flora conditions, were used to investigate the pathogenesis of scrapie after intracerebral or intraperitoneal inoculation. Time in days to onset of clinical signs (Stage I), to endstage (Stage II), and the time interval between Stage I and Stage II were compared among groups. In addition, scrapie agent titers in spleen were determined at 28 and 90 days after infection, as were agent titers in spleen and brain at Stage II. Three-way analysis of variance indicated that the bacterial flora, the presence or absence of a thymus, and the route of agent inoculation interact to produce significant differences in the pathogenesis of disease. The three factors in the experimental design also influenced the spleen titers of scrapie infectivity. The variation in scrapie pathogenesis among the groups of mice is likely to be mediated by differences in their reticuloendothelial systems. These differences may alter the agent's adsorption in spleen and/or route of transport from spleen to brain.

The microbiota–microglia axis in central nervous system disorders

“…A subsequent study by Wade at al. describes an extension in the survival of GF mice only upon intraperitoneal, but not intracerebral, injection of ME7 scrapie prions, when compared to mice with a defined microbiota comprising particular bacterial species of Clostridium, Bacillus, Lactobacillus, and Bacteroides (129). However, a more recent study by Bradford et al shows that the exposure to prions by intraperitoneal or intracerebral injection did not affect the susceptibility or survival of the GF compared to SPF mice.…”

Prion disease pathogenesis in the absence of the commensal microbiota

“…Survival times were reported to be extended in the germ-free mice, but from the data presented it is uncertain whether this effect was significant [ 31 ]. In a later study, Wade and colleagues compared prion disease survival times after IC or IP injection with ME7 scrapie prions in germ-free mice with those colonized with a highly restricted Gram-positive bacterial microflora [ 32 ]. Consistent with data presented in the current study, survival times after IC prion exposure were not influenced by the microbiological status of the mice, but a prolongation was observed in the germ-free mice after IP exposure [ 32 ].…”

“…In a later study, Wade and colleagues compared prion disease survival times after IC or IP injection with ME7 scrapie prions in germ-free mice with those colonized with a highly restricted Gram-positive bacterial microflora [ 32 ]. Consistent with data presented in the current study, survival times after IC prion exposure were not influenced by the microbiological status of the mice, but a prolongation was observed in the germ-free mice after IP exposure [ 32 ]. Precise explanations for the inconsistencies between data in this study and the current study are uncertain, but a highly restricted Gram-positive bacterial microflora similar to that used as a control in the Wade study can itself influence microglial status [ 28 ].…”

The influence of the commensal and pathogenic gut microbiota on prion disease pathogenesis

“…However, it is uncertain from data presented whether this effect was significant (Lev et al, 1971) (Table 3). Furthermore, a subsequent study by Wade et al (1986) did not observe a difference in survival time after intracerebral injection of ME7 scrapie prions into germ-free mice, but a prolongation was observed after intraperitoneal exposure (Table 3). The inconsistencies between these studies are difficult to explain.…”

“…(Lev et al, 1971). †In the study by Wade and colleagues, the effects in germ-free mice were compared with those colonized with a restricted, defined Gram-positive bacterial flora comprising of particular species of Clostridium, Bacillus, Lactobacillus and Bacteroides (Wade et al, 1986). ‡Incidence: no.…”