Kelly Anderson

Aerosol Transmission of Chronic Wasting Disease in White-Tailed Deer

ABSTRACT While the facile transmission of chronic wasting disease (CWD) remains incompletely elucidated, studies in rodents suggest that exposure of the respiratory mucosa may be an efficient pathway. The present study was designed to address this question in the native cervid host. Here, we demonstrate aerosol transmission of CWD to deer with a prion dose >20-fold lower than that used in previous oral inoculations. Inhalation of prions may facilitate transmission of CWD and, perhaps, other prion infections.

Mother to Offspring Transmission of Chronic Wasting Disease in Reeves’ Muntjac Deer

The horizontal transmission of prion diseases has been well characterized in bovine spongiform encephalopathy (BSE), chronic wasting disease (CWD) of deer and elk and scrapie of sheep, and has been regarded as the primary mode of transmission. Few studies have monitored the possibility of vertical transmission occurring within an infected mother during pregnancy. To study the potential for and pathway of vertical transmission of CWD in the native cervid species, we used a small cervid model–the polyestrous breeding, indoor maintainable, Reeves’ muntjac deer–and determined that the susceptibility and pathogenesis of CWD in these deer reproduce that in native mule and white-tailed deer. Moreover, we demonstrate here that CWD prions are transmitted from doe to fawn. Maternal CWD infection also appears to result in lower percentage of live birth offspring. In addition, evolving evidence from protein misfolding cyclic amplification (PMCA) assays on fetal tissues suggest that covert prion infection occurs in utero. Overall, our findings demonstrate that transmission of prions from mother to offspring can occur, and may be underestimated for all prion diseases.

Susceptibility of domestic cats to chronic wasting disease

ABSTRACT Domestic and nondomestic cats have been shown to be susceptible to feline spongiform encephalopathy (FSE), almost certainly caused by consumption of bovine spongiform encephalopathy (BSE)-contaminated meat. Because domestic and free-ranging nondomestic felids scavenge cervid carcasses, including those in areas affected by chronic wasting disease (CWD), we evaluated the susceptibility of the domestic cat (Felis catus) to CWD infection experimentally. Cohorts of 5 cats each were inoculated intracerebrally (i.c.) or orally (p.o.) with CWD-infected deer brain. At 40 and 42 months postinoculation, two i.c.-inoculated cats developed signs consistent with prion disease, including a stilted gait, weight loss, anorexia, polydipsia, patterned motor behaviors, head and tail tremors, and ataxia, and the cats progressed to terminal disease within 5 months. Brains from these two cats were pooled and inoculated into cohorts of cats by the i.c., p.o., and intraperitoneal and subcutaneous (i.p./s.c.) routes. Upon subpassage, feline CWD was transmitted to all i.c.-inoculated cats with a decreased incubation period of 23 to 27 months. Feline-adapted CWD (FelCWD) was demonstrated in the brains of all of the affected cats by Western blotting and immunohistochemical analysis. Magnetic resonance imaging revealed abnormalities in clinically ill cats, which included multifocal T2 fluid attenuated inversion recovery (FLAIR) signal hyperintensities, ventricular size increases, prominent sulci, and white matter tract cavitation. Currently, 3 of 4 i.p./s.c.- and 2 of 4 p.o. secondary passage-inoculated cats have developed abnormal behavior patterns consistent with the early stage of feline CWD. These results demonstrate that CWD can be transmitted and adapted to the domestic cat, thus raising the issue of potential cervid-to-feline transmission in nature.

MUCOSAL IMMUNIZATION TO PREVENT CHRONIC WASTING DISEASE (CWD) IN DEER

P4-204 NEURO-PEPTIDE TREATMENT WITH CEREBROLYSIN IMPROVES THE SURVIVAL OF NEURAL STEM CELL GRAFTS IN THE APP TRANSGENIC MODEL OFALZHEIMER’S DISEASE Edward Rockenstein, Paula Desplats, Michael Mante, Jazmin Florio, Scott Anderson, Dieter Meier, Stefan Winter, Anthony Adame, Herbert Moessler, Eliezer Masliah, University of California San Diego, La Jolla, California, United States; University of California San Diego, La Jolla, California, United States; University of California San Diego, La Jolla, California, United States; University of California San Diego, La Jolla, California, United States; Ever Neuro Pharma GmbH, Unterach, Austria; Ever Neuro Pharma GmbH, Unterach, Austria; Ever Neuro Pharma GmbH, San Diego, California, United States; University of California San Diego, La Jolla, California, United States. Contact e-mail: erockenstein@ucsd.edu

Active immune intervention for prionoses in deer

micromolar range. We previously reported that the drug showed neuroprotective potential against amyloid toxicity in mice. In particular, ANAVEX2-73 attenuated the oxidative stress, caspases induction, cellular loss and learning and memory deficits observed in mice one week after the icv injection of an oligomeric preparation of amyloid beta-(25-35) peptide (Abeta 25-35) (Villard et al., J Psychopharmacol 2011). More recently, we reported that ANAVEX2-73 blocked the Abeta 25-35 -induced P-Akt decrease and P-GSK-3beta increase, indicating activation of the PI3K neuroprotective pathway (Lahmy et al., Soc Neurosci Abstr 2011). As a result, ANAVEX2-73 attenuated, in the dose-range tested, the hyperphosphorylation of Tau on physiological epitopes (AT-8 antibody clone) and on pathological epitopes (AT-100 clone). ANAVEX273 also decreased the Abeta 25-35 -induced endogenous Abeta 1-42 seeding. The drug may thus act as a disease-modifying agent not only protecting brain cells from toxicity but also contributing to decrease Tau pathology and amyloid load. Methods:We here analyzed the impact of administration schedule and combination with donepezil on the efficacy of the drug. Results: ANAVEX2-73 (0.1, 0.3 mg/kg ip), administered once a day between day -7 and day -1 before Abeta 25-35 (day 0), blocked the Abeta 25-35 -induced memory deficits (spontaneous alternation in the Y maze and passive avoidance response) and lipid peroxidation in the hippocampus 7 days after Abeta 25-35. ANAVEX2-73 (0.3 mg/kg ip) was also effective when it was administered once a day between day 7 and day 13 after Abeta 25-35 (on day 0), on memory deficits and lipid peroxidation increase measured 14 days after Abeta 25-35. In combination with donepezil (0.25, 0.5 mg/kg ip), the effects appeared synergistic, since the combination of the lowest non-effective doses (0.25 donepezil + 0.1 ANAVEX2-73) led to a significant protection on all parameters examined. Combination studies with memantine are in progress. Conclusions: These results showed a good preventing and restorating efficacy for the compound in the Abeta 25-35 model in mice and showed a preserved efficacy in combination with the reference acetylcholinesterase inhibitor.