Since 1995, more than 100 transgenic (Tg) mouse models of Alzheimer’s disease (AD) have been generated in which mutant amyloid precursor protein (APP) or APP/presenilin 1 (PS1) cDNA is overexpressed (1st generation models). Our results suggest that, compared to the rat and rabbit brains, connections between the hippocampal formation and presubiculum are highly organized and characteristic in the marmoset brain. We also found that the cells of origin of the subiculo-presubicular projections were localized in the middle part along the superficial-to-deep axis of the pyramidal cell layer of the distal subiculum in the marmoset, which was similar to that in both rats and rabbits. We demonstrated the presence of a direct projection from the CA1 pyramidal cell layer to the deep layers of the presubiculum in the marmoset, which was previously identified in the rabbit brain, but not in the rat. Here, we investigated the neuronal connectivity of the marmoset, especially focusing on the connectivity between the hippocampal formation and the presubiculum, using retrograde and anterograde tracers (cholera toxin-B subunit and biotin dextran amine). The marmoset (a New World monkey) has recently received much attention as an experimental animal model however, little is known about the connectivity of limbic regions, including cortical and hippocampal memory circuits, in the marmoset. Furthermore, the behavioral changes observed might be directly extrapolated to humans and contribute to better understanding of the mechanisms underlying neurodegenerative disorders. This system will allow quantification of individual captive group animals, facilitating automatic measurement of social behavior. Location preferences and distances between individuals were calculated using 3D trajectories, and grooming was detected using deep learning. Each marmoset was identified using deep learning facial recognition (accuracy ≥ 97%). Here, we developed a new behavioral analysis system for three-dimensional (3D) trajectories of independently free-moving multiple individuals by combining video tracking, 3D coordinates detected using light detection and ranging (Lidar), and facial recognition. However, behavioral measurements, including assessments of sociality of free-moving group animals, have not been conducted in marmosets. The common marmoset ( Callithrix jacchus ) is a useful model in this regard. We intend to make our marmoset model available to the research community to facilitate the global fight against AD.Īccurate assessment of behavioral changes and social interactions in mammalian models is necessary to elucidate the pathogenesis of neurological disorders. To our knowledge, this is the first non-human primate model of familial AD. Fibroblasts obtained from newborn marmosets exhibited uncleaved full-length presenilin 1 protein (PS1) caused by the perturbation of PS1 endoproteolysis as well as an increased ratio of Abeta42/Abeta40 production, a signature of familial AD pathogenesis. Indeed, whole genome sequencing and other analyses illustrated an absence of off-target effects and an apparent absence of mosaicism. To this end, TALEN exhibits high genome-editing efficacy, generates few off-target effects, and produces minimal mosaicism. We used Transcription Activator-Like Effector Nuclease (TALEN) to destroy the 3' splice site of exon 9 in the marmoset PSEN1 gene. Such DeltaE9 mutations have been reported to cause early on-set familial AD (references 1-5). Here, we describe the generation of three mutant marmoset individuals in which exon 9 of PSEN1 gene product has been deleted (PSEN1-DeltaE9). Despite extensive research efforts, no effective measures are available to facilitate the prevention or treatment of AD, which is due in part to a lack of animal models able to closely replicate a human-like disease state. ![]() Alzheimer's disease (AD) is a major cause of dementia, with the number of patients with this condition anticipated to exceed 50 million worldwide in the near future.
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