Propagation of distinct CWD prion strains during peripheral and intracerebral challenges of gene-targeted mice.

Since prion diseases result from infection and neurodegeneration of the central nervous system (CNS), experimental characterizations of prion strain properties customarily rely on the outcomes of intracerebral challenges. However, natural transmission of certain prions, including those causing chronic wasting disease (CWD) in elk and deer, depends on propagation in peripheral host compartments prior to CNS infection. Using gene-targeted GtE and GtQ mice, which accurately control cellular elk or deer PrP expression, we assessed the impact that peripheral or intracerebral exposures play on CWD prion strain propagation and resulting CNS abnormalities. Whereas oral and intraperitoneal transmissions produced identical neuropathological outcomes in GtE and GtQ mice and preserved the naturally convergent conformations of elk and deer CWD prions, intracerebral transmissions generated CNS prion strains with divergent biochemical properties in GtE and GtQ mice that were changed compared to their native counterparts. While CWD replication kinetics remained constant during iterative peripheral transmissions and brain titers reflected those found in native hosts, serial intracerebral transmissions produced 10-fold higher prion titers and accelerated incubation times. Our demonstration that peripherally and intracerebrally challenged Gt mice develop dissimilar CNS diseases which result from the propagation of distinct CWD prion strains points to the involvement of tissue-specific cofactors during strain selection in different host compartments. Since peripheral transmissions preserved the natural features of elk and deer prions, whereas intracerebral propagation produced divergent strains, our findings illustrate the importance of experimental characterizations using hosts that not only abrogate species barriers but also accurately recapitulate natural transmission routes of native strains.

Aversive conditioning in the tardigrade, Dactylobiotus dispar.

Defensive responses to threatening events in the environment are displayed by a vast number of animals, both vertebrate and invertebrate. These defensive responses can be associated with salient neutral stimuli that are present along with the threatening stimulus. This is referred to as aversive conditioning. Animals with more simple nervous systems, such as Aplysia, C elegans, and Drosophila, have facilitated identification of some the physiological processes that support aversive conditioning. Perhaps even more basic information regarding the neurobiology of learning and memory may be gleaned from animals that have special characteristics not found in other species. Tardigrades, also known as "water bears," are microscopic eight-legged animals that live in various aquatic and terrestrial environments. They are known for their resilience to extreme conditions because of their ability to enter a cryptobiotic "tun" state during which they turn off their metabolism. Thus, tardigrades present an ideal model to study the metabolic requirements for memory storage. However, there is no prior research on tardigrade learning and memory. The purpose of this study was to demonstrate aversive conditioning in a tardigrade species, Dactylobiotus dispar. Associative learning was confirmed by numerous control conditions (unconditioned stimulus [US] only, conditional stimulus [CS] only, backward pairing, random pairing). Short-term memories were formed after a single pairing of the CS and US. This research introduces an important new animal model to the study of the neurobiology of aversive conditioning with important ramifications for understanding the metabolic influences on learning and memory. (PsycINFO Database Record (c) 2019 APA, all rights reserved).