Why individuals with Down syndrome (DS) are more susceptible to SARS-CoV-2–induced neuropathology remains elusive. Choroid plexus (ChP) plays critical roles in barrier function and immune response modulation and expresses the ACE2 receptor and the chromosome 21–encoded TMPRSS2 protease, suggesting its substantial role in establishing SARS-CoV-2 infection in the brain. To explore this, we established brain organoids from DS and isogenic euploid iPSC that consist of a core of functional cortical neurons surrounded by a functional ChP-like epithelium (ChPCOs). DS-ChPCOs recapitulated abnormal DS cortical development and revealed defects in ciliogenesis and epithelial cell polarity in ChP-like epithelium. We then demonstrated that the ChP-like epithelium facilitates infection and replication of SARS-CoV-2 in cortical neurons and that this is increased in DS. Inhibiting TMPRSS2 and furin activity reduced viral replication in DS-ChPCOs to euploid levels. This model enables dissection of the role of ChP in neurotropic virus infection and euploid forebrain development and permits screening of therapeutics for SARS-CoV-2–induced neuropathogenesis.
Aim: This study aimed to evaluate the protective effect of edible bird's nest (EBN) supplement on the uteri of rats exposed to lead acetate (LA) toxicity. Materials and Methods: Five treatment groups were established as follows: Group 1 (C), which was given distilled water; Group 2 (T0), which was administered with LA (10 mg/kg body weight [BW]); and Groups 3 (T1), 4 (T2), and 5 (T3), which were given LA (10 mg/kg BW) plus graded concentrations of 30, 60, and 120 mg/kg BW of EBN, respectively, for days. Rats were euthanized at week 5 to collect blood for superoxide dismutase (SOD) assay, and uterus for histomorphological study and expression analyses of epidermal growth factor (EGF), vascular endothelial growth factor (VEGF), and proliferating cell nuclear antigen (PCNA). Results: Results revealed that LA causes destruction of uterine lining cells and necrosis of uterine glands of exposed rats without EBN supplement while the degree of damage decreased among EBN treated groups; T3 showed the highest ameliorating effect against LA toxicity, as well as an increased number of uterine glands. Increased levels of SOD were also achieved in EBN supplemented groups than the controls. Results of immunohistochemistry showed significantly higher expressions of EGF, VEGF, and PCNA levels (p<0.05) in T3 compared to other treatments. EBN maintained upregulation of antioxidant – reactive oxygen species balance. Conclusion: The findings showed that EBN could ameliorate the detrimental effects of LA toxicity on the uterus possibly by enhancing enzymatic antioxidant (SOD) activity as well as expressions of EGF, VEGF, and PCNA with cell proliferation roles.
In response to the scarcity of advanced in vitro models dedicated to human CNS white matter research, we present a protocol to generate neuroectoderm-derived embedding-free human brain organoids enriched with oligodendrocytes. We describe steps for neuroectoderm differentiation, development of neural spheroids, and their transferal to Matrigel. We then detail procedures for the development, maturation, and application of oligodendrocyte-enriched brain organoids. The presence of myelin-producing cells makes these organoids useful for studying human white matter diseases, such as leukodystrophy.