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Scientists have identified a stress-induced molecular pathway that reveals new molecular targets for treating neuropsychiatric systemic lupus erythromatosus (NPSLE). The investigators conducted experiments on mice models and human patients to show that the medial prefrontal cortex is affected in this severe autoimmune disorder and the levels of IL-12 and IL-23 are upregulated that caused microglial activation. Blocking IL-12 and IL-23 pathways in these sleep-deprived mice models of NPSLE inhibits stress-induced neuropsychiatric symptoms.
Memory B cells in the lungs consist of two transcriptionally distinct subsets localized strategically in the bronchial niche. ‘‘Bona fide’’ virus-specific memory B lymphocytes, dominate recall responses and harbor specific affinity for the triggering virus while ‘‘bystander’’ non-specific memory B lymphocytes, locally retain antigens as immune complexes and expand the diversity of the initial B cell repertoire, in addition to enabling cross-reactions of different bona fide memory B cell populations against several types of viruses.
Researchers have engineered gut bacteria with data logger functionality to enable them to monitor which genes are active in the bacteria as they traverse the gut. These sentinel microorganisms tested in mice and limited to engineered E. coli in the current study, offer insights that could help develop noninvasive, diagnostic, microbial sensors that could uncover early symptoms of intestinal disease or assess the effect of diet or therapies on health.
Injection of NYX-783, a positive modulator of the excitatory glutamatergic receptor NMDAR, before fear extinction therapy resulted in the successful extinction of PTSD memories and prevented spontaneous recovery in mouse models of PTSD. The drug was more effective in female mice, suggesting differential sensitivity of NMDAR modulators in males and females. When the activity of endogenous BDNF was blocked in the mouse brain, the PTSD memory underwent spontaneous recovery even after successful extinction indicating BDNF is required for for the inhibitory effect of NYX-783 on spontaneous recovery.
High-grade serous ovarian carcinoma (HGSOC) creates an immunosuppressive tumor microenvironment that renders this form of malignancy insensitivity to checkpoint inhibitor immunotherapies. A new study shows combining an oral inhibitor of a gene that encodes a focal adhesion kinase that is elevated in nearly 70% of patients with HGSOC, together with an antibody that blocks the TIGIT immunoreceptor’s function, generates a significant antitumor response and increased survival time of a mouse model of the lethal cancer.
A localized signaling system can initiate an action potential in an axon challenging a core tenet of how neurons work. The study showed that acetylcholine can trigger dopamine release directly in the striatum without action potentials from cell bodies in the midbrain. When the researchers disabled acetylcholine receptors on dopamine neurons, dopamine levels in the mouse striatum dropped. The findings could lead to new treatments for Parkinson’s disease that restore dopamine levels by targeting acetylcholine neurons.
Researchers at the University of Osaka in Japan have demonstrated, in a preclinical study on human autopsy samples and in a disease-relevant rat model, that treatment with a monoclonal antibody against against a glycoprotein reduces the expression of CXCL2 in macrophages. The researchers observed fewer neutrophils at the damaged nerves, less astrocytic death, and decreased movement and pain symptoms associated with neuromyelitis optica.
Metastatic melanoma cells recovered from human brains and grown in tissue cultures make roughly three times as much amyloid beta as cancer cells that have spread to other parts of the body, a new study finds. The study shows treatment of mouse models of melanoma brain metastasis with a pharmacological inhibitor that reduces levels of amyloid beta in the brain, decreases the size of brain melanoma metastases by about half.
A new study on mice shows that targeting IRAK4, the master kinase that drives innate immune response and inflammation, decreases tumor fibrosis and revitalizes intratumoral T cells, increasing the sensitivity of pancreatic cancers to chemotherapy and checkpoint immunotherapy. The preclinical study provides the scientific rationale for combining an IRAK4 inhibitor with chemotherapy and checkpoint immunotherapy in clinical trials for patients with pancreatic ductal adenocarcinoma.
A new study shows treatment of model mice during the five weeks following birth with rapamycin, a drug that blocks a neurodevelopmental pathway called mTOR signaling, is sufficient to ensure the development and maintenance of normal social behavior—the primary diagnostic criterion for autism spectrum disorders (ASD), whereas treatment with the drug, even into adulthood, does not remedy repetitive behaviors and behavioral inflexibility—the other diagnostic criteria for ASD.