Cerebral amyloid plaques are a conspicuous pathological feature in mice infected with certain strains of scrapie. The origin of the amyloid protein in these plaques, whether it is locally or systemically synthesized, and the mechanisms leading to its deposition are not known. The frequency of plaques and their distribution in the brain are greatly influenced by the route of injection of the scrapie inoculum. Intracerebral injection consistently results in greater numbers of plaques than are obtained if the same inoculum is introduced peripherally. Following intracerebral injection, plaques are commonly seen in areas close to the lateral ventricles, for example the corpus callosum and hippocampus, whereas they are absent from these areas with peripheral routes. Furthermore, when left- and right- sided intracerebral injections are compared, plaques are more frequent on the side of injection. These results suggest that the distribution of amyloid plaques is influenced either by the localization of some component of the inoculum or by traumatic damage at injection. The most plausible explanation is that amyloid deposition is associated with local concentrations of scrapie infectivity and that the amyloid protein originates in the brain.

Amyloidosis↗

PubMedDate not supplied

Effects of age on cerebral amyloid plaques in murine scrapie.

The frequency of cerebral amyloid plaques in murine scrapie was not influenced by the age of the mouse at injection in a study using several combinations of agent strain and mouse strain. In addition amyloid plaques were not seen in a series of extremely old uninfected mice.

Age Factors↗

PubMedDate not supplied

Retinopathy in mice with experimental scrapie.

Scrapie is a naturally occurring neurological disease of adult sheep and goats with an incubation period of several years. Some strains of the causal agent can infect laboratory mice in which the incubation period, as well as the severity and distribution of vacuolar degeneration in the brain, varies according to the strain of the agent and the genotype of the mouse. Retinopathy, involving the partial or complete loss of the photoreceptor layer, was observed in a number of murine scrapie models but was absent in others. The severity of retinopathy depended on both the strain of scrapie and the genotype of mouse used. Some scrapie strains (22C, 87A and 87V) produced minimal or no retinal pathology, others (ME7, 22A and 22L) produced changes in the retinae of only certain mouse genotypes, while the strains 79A and 139A produced degeneration of the photoreceptor layer in every mouse genotype investigated. The severity of retinopathy in the various models did not correlate with the overall intensity of vacuolar degeneration in the brain, with the severity of vacuolation in the centres in the brain controlling pupillary constriction, or with the incubation period.

Animals↗

PubMedDate not supplied

Evidence that transmissible mink encephalopathy agent is biologically inactive in mice.

Transmissible mink encephalopathy (TME) is probably a form of the sheep disease, scrapie, introduced by accidentally feeding mink with scrapie-infected sheep tissues. Although no successful transmissions of TME to mice have been achieved previous work has involved various limitations. To maximize the possibility of transmission, 176 mice, representing 14 different genotypes mostly not previously tested with TME, were injected with TME-infected mink brain from three sources with different histories. No scrapie-like disease was detected clinically or histologically in these mice or in a further 111 which were subsequently injected with brain or spleen material from 10 of the TME-injected mice killed when senile. Furthermore, a series of experiments involving seven strains of scrapie, demonstrated that prior injection of mice with TME failed to affect the normal progress of scrapie infection indicating that TME agent had not occupied scrapie replication sites or otherwise influenced the pathogenesis of scrapie. The overall conclusion from these experiments is that TME is biologically inactive in mice. Although many strains of natural scrapie can be transmitted to laboratory mice, this has not been possible with all strains and it is concluded that one or more of such strains is likely to be the cause of TME in mink.

Animals↗

PubMedDate not supplied

Immunostaining of scrapie cerebral amyloid plaques with antisera raised to scrapie-associated fibrils (SAF).

Brain sections from 16 different mouse scrapie models were immunostained with antisera to scrapie-associated fibrils (SAF) from three experimental scrapie sources (hamster 263K, mouse ME7 and mouse 22L). These models involved seven strains of scrapie injected intracerebrally or intraperitoneally into a range of inbred mouse strains, producing a wide variety of neuropathological changes. The only brain structures which were positively immunostained were amyloid plaque cores in those models in which plaques could be readily identified using traditional amyloid stains. The intensity of immunostaining correlated with the density of amyloid in the cores, as detected by Congo red and thioflavine S staining. No differences in immunostaining specificity were found between antisera or between plaques in different combinations of scrapie strain and mouse genotype. There were also no differences in immunoreactivity between plaques in different parts of the brain. These results strongly suggest that SAF and histologically detectable amyloid in scrapie mice are derived from the same precursor protein. Scrapie-associated cerebrovascular amyloid and plaques in sheep and goats also gave positive immunostaining with SAF antisera, although the lesions in the natural disease could only be stained after formic acid pretreatment. Senile plaques in Alzheimer's disease and Down's syndrome, although structurally similar to scrapie amyloid plaques, were found to be completely negative for SAF, in agreement with previous biochemical and immunocytochemical findings.

Amyloid↗

PubMedDate not supplied

The correlation of electroretinographic and histopathological findings in the eyes of mice infected with the 79A strain of scrapie.

Retinal degeneration was produced using the 79A strain of scrapie injected intracerebrally into mice of the MM inbred strain, and studied by electroretinography and light and electron microscopy during the preclinical and clinical phases of the disease. The changes in the electroretinogram (ERG), detectable in some mice at 118 days postinjection (d.p.i.), appeared to coincide with the earliest morphological evidence of photoreceptor damage. In the early stages there was a progressive reduction of b-wave amplitude without marked loss of retinal sensitivity or significant change in a- and b-wave peak implicit times. Extinction of the ERG, observed in half the mice examined at 144 d.p.i., approximated to a stage of the retinopathy in which the outer nuclear layer was reduced to about four rows of nuclei. Early morphological changes suggested that the primary lesion involved the integrity of the photoreceptor as a whole, the electrophysiological findings reflecting a primary loss of light sensitive tissue rather than impairment of the transduction mechanism or neurotransmission.

Animals↗