As the primary interface with the environment, the lungs require a robust local immune defense against pathogens. In a non-human primate model of SARS-CoV-2 Omicron infection, we used scRNA-seq, spatial transcriptomics, and immunoassays to investigate localized immune memory. Our results demonstrated established adaptive responses in lung tissue and medLNs, with significant activation of tissue-resident T cells and GC (germinal center) B cells.
View Article and Find Full Text PDFCerebrospinal fluid (CSF) in the subarachnoid space around the brain drains to lymph nodes in the neck, but the connections and regulation have been challenging to identify. Here we used fluorescent tracers in Prox1-GFP lymphatic reporter mice to map the pathway of CSF outflow through lymphatics to superficial cervical lymph nodes. CSF entered initial lymphatics in the meninges at the skull base and continued through extracranial periorbital, olfactory, nasopharyngeal and hard palate lymphatics, and then through smooth muscle-covered superficial cervical lymphatics to submandibular lymph nodes.
View Article and Find Full Text PDFMol Ther Nucleic Acids
December 2024
Oxidative stress plays an essential role in the progression of Alzheimer's disease (AD), the most common age-related neurodegenerative disorder. Streptozotocin (STZ)-induced abnormal brain insulin signaling and oxidative stress play crucial roles in the progression of Alzheimer's disease (AD)-like pathology. Peroxiredoxins (Prxs) are associated with protection from neuronal death induced by oxidative stress.
View Article and Find Full Text PDFGlutamatergic mossy cells (MCs) mediate associational and commissural connectivity, exhibiting significant heterogeneity along the septotemporal axis of the mouse dentate gyrus (DG). However, it remains unclear whether the neuronal features of MCs are conserved across mammals. This study compares the neuroanatomy of MCs in the DG of mice and monkeys.
View Article and Find Full Text PDFThe role of death-associated protein kinase1 (DAPK1) in post-stroke functional recovery is controversial, as is its mechanism of action and any neural remodeling effect after ischemia. To assess the debatable role of DAPK1, we established the middle cerebral artery occlusion (MCAo) model in DAPK1 knockout mice and Sprague-Dawley (SD) rats. We identified that the genetic deletion of the DAPK1 as well as pharmacological inhibition of DAPK1 showed reduced brain infarct volume and neurological deficit.
View Article and Find Full Text PDFCharacterizing the host response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at the molecular level is necessary to understand viral pathogenesis and identify clinically relevant biomarkers. However, in humans, the pulmonary host response during disease onset remains poorly understood. Herein, we utilized a spatial transcriptome atlas to identify pulmonary microstructure-specific COVID-19 gene signatures during the acute phase of lung infection in cynomolgus macaques.
View Article and Find Full Text PDFPreclinical ischemic stroke studies extensively utilize the intraluminal suture method of middle cerebral artery occlusion (MCAo). General anesthesia administration is an essential step for MCAo, but anesthetic agents can lead to adverse effects causing death and making a considerable impact on inducing cerebral ischemia. The purpose of this study was to comparatively assess the effect of isoflurane and xylazine on transient cerebral ischemia in a mouse model of MCAo.
View Article and Find Full Text PDFTill date, researchers have been developing animal models of Alzheimer's disease (AD) in various species to understand the pathological characterization and molecular mechanistic pathways associated with this condition in humans to identify potential therapeutic treatments. A widely recognized AD model that mimics the pathology of human AD involves the intracerebroventricular (ICV) injection with streptozotocin (STZ). However, ICV injection as an invasive approach has several limitations related to complicated surgical procedures.
View Article and Find Full Text PDFInt J Environ Res Public Health
December 2022
Coronavirus disease 2019 (COVID-19) led to the loss of lives and had serious social and economic effects. Countries implemented various quarantine policies to reduce the effects. The countries were divided into low- and high-risk groups based on the differences in quarantine policies and their levels of infection.
View Article and Find Full Text PDFParkinsons Dis
November 2022
Background In tandem stenoses, nonhyperemic pressure ratio pullback is the preferred method to fractional flow reserve (FFR), based on the assumption of stable resting coronary flow. This study aimed to evaluate temporal changes of coronary circulatory indexes in tandem stenoses before and after angioplasty for proximal stenosis. Methods and Results Coronary tandem stenoses were created by porcine restenosis model with 2 bare metal stents in the left anterior descending artery.
View Article and Find Full Text PDFExp Neurobiol
October 2020
Symptoms of Parkinson's disease (PD) caused by loss of dopaminergic neurons are accompanied by movement disorders, including tremors, rigidity, bradykinesia, and akinesia. Non-human primate (NHP) models with PD play an essential role in the analysis of PD pathophysiology and behavior symptoms. As impairments of hand dexterity function can affect activities of daily living in patients with PD, research on hand dexterity function in NHP models with chronic PD is essential.
View Article and Find Full Text PDFExp Neurobiol
August 2020
Ischemic stroke results from arterial occlusion and can cause irreversible brain injury. A non-human primate (NHP) model of ischemic stroke was previously developed to investigate its pathophysiology and for efficacy testing of therapeutic candidates; however, fine motor impairment remains to be well-characterized. We evaluated hand motor function in a cynomolgus monkey model of ischemic stroke.
View Article and Find Full Text PDFAberrant brain insulin signaling plays a critical role in the pathology of Alzheimer's disease (AD). Mitochondrial dysfunction plays a role in the progression of AD, with excessive mitochondrial fission in the hippocampus being one of the pathological mechanisms of AD. However, the molecular mechanisms underlying the progression of AD and mitochondrial fragmentation induced by aberrant brain insulin signaling in the hippocampal neurons are poorly understood.
View Article and Find Full Text PDFTo date, researchers have developed various animal models of Alzheimer's disease (AD) to investigate its mechanisms and to identify potential therapeutic treatments. A widely recognized model that mimics the pathology of human sporadic AD involves intracerebroventricular (ICV) injection with streptozotocin (STZ). However, ICV injections are an invasive approach, which creates limitations in generalizing the results.
View Article and Find Full Text PDFPhysical exercise has long been recommended as a treatment for osteoarthritis (OA), though its effects vary based on the exercise protocol. Here, we examined whether environmental lighting conditions influence the anti-inflammatory benefits of exercise in a rat model of OA. Moderate-intensity treadmill exercise (Ex) was performed for six weeks under a 12:12 h light/dark (L/D) cycle, and compared against rats housed in a 24 h continuous light (L/L) environment.
View Article and Find Full Text PDFPigs are often selected for large animal models including for neuroscience and behavioral research, because their anatomy and biochemistry are similar to those of humans. However, behavioral assessments, in combination with objective long-term monitoring, is difficult. In this study, we introduced an automated video tracking system which was previously used in rodent studies, for use with pig models.
View Article and Find Full Text PDFMitochondria continuously fuse and divide to maintain homeostasis. An impairment in the balance between the fusion and fission processes can trigger mitochondrial dysfunction. Accumulating evidence suggests that mitochondrial dysfunction is related to neurodegenerative diseases such as Parkinson's disease (PD), with excessive mitochondrial fission in dopaminergic neurons being one of the pathological mechanisms of PD.
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