Cognition is a complex brain function that represents processes such as learning and memory, attention, working memory, and executive functions amongst others. Impairments in cognition are prevalent in many neuropsychiatric and neurological disorders with few viable treatment options. The development of new therapies is challenging, and poor efficacy in clinical development continues to be one of the most consistent reasons compounds fail to advance, suggesting that traditional animal models are not predictive of human conditions and behavior. An effort to improve the construct validity of neuropsychological testing across species with the intent of facilitating therapeutic development has been strengthening over recent years. With an emphasis on understanding the underlying biology, optimizing the use of appropriate systems (e.g., transgenic animals) to model targeted disease states, and incorporating non-rodent species (e.g., non-human primates) that may enable a closer comparison to humans, an improvement in the translatability of the results will be possible. This chapter focuses on some promising translational cognitive paradigms for use in rodents, non-human primates, and humans.
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http://dx.doi.org/10.1007/978-3-319-16522-6_2 | DOI Listing |
Drugs
January 2025
Palliative Medicine, Geisinger Medical Center, Danville, PA, USA.
Buprenorphine is an agonist at the mu opioid receptor (MOR) and antagonist at the kappa (KOR) and delta (DOR) receptors and a nociceptin receptor (NOR) ligand. Buprenorphine has a relatively low intrinsic efficacy for G-proteins and a long brain and MOR dwell time. Buprenorphine ceiling on respiratory depression has theoretically been related multiple factors such as low intrinsic efficacy at MOR, binding to six-transmembrane MOR and interactions in MOR/NOR heterodimers.
View Article and Find Full Text PDFTranspl Int
January 2025
Center for Transplantation Sciences, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States.
An overview is provided of the evolution of strategies towards xenotransplantation during the past almost 40 years, focusing on advances in gene-editing of the organ-source pigs, pre-transplant treatment of the recipient, immunosuppressive protocols, and adjunctive therapy. Despite initial challenges, including hyperacute rejection resulting from natural (preformed) antibody binding and complement activation, significant progress has been made through gene editing of the organ-source pigs and refinement of immunosuppressive regimens. Major steps were the identification and deletion of expression of the three known glycan xenoantigens on pig vascular endothelial cells, the transgenic expression of human "protective" proteins, e.
View Article and Find Full Text PDFSci Rep
January 2025
Department of Neurosurgery of the Second Affiliated Hospital, Interdisciplinary Institute of Neuroscience and Technology, School of Medicine, Zhejiang University, Hangzhou, China.
Horizontal connections in anterior inferior temporal cortex (ITC) are thought to play an important role in object recognition by integrating information across spatially separated functional columns, but their functional organization remains unclear. Using a combination of optical imaging, electrophysiological recording, and anatomical tracing, we investigated the relationship between stimulus-response maps and patterns of horizontal axon terminals in the macaque ITC. In contrast to the "like-to-like" connectivity observed in the early visual cortex, we found that horizontal axons in ITC do not preferentially connect sites with similar object selectivity.
View Article and Find Full Text PDFAntiviral Res
January 2025
CIRI, Centre International de Recherche en Infectiologie, INSERM U1111, CNRS, UMR5308, Univ Lyon, Université Claude Bernard Lyon 1, École Normale Supérieure de Lyon, 21 Avenue Tony Garnier, 69007 Lyon, France.
Nipah virus (NiV) is a lethal zoonotic paramyxovirus that can be transmitted from person to person through the respiratory route. There are currently no licensed vaccines or therapeutics. A lipopeptide-based fusion inhibitor was developed and previously evaluated for efficacy against the NiV-Malaysia strain.
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