Lesion Induced Cellular Models
Creative Biolabs has been focusing on neuroscience research for years and has rich project experience. We integrate global resources and establish advanced technology platforms to provide our clients with convenient lesion induced cellular models and one-stop services. We have extensive experience in lesion induced cellular models and here we will introduce two of them briefly: excitotoxicity in vitro models and stress granule formation in vitro models.
Excitotoxicity In Vitro Models
Glutamate is the principal neurotransmitter in the adult central nervous system. In addition to being required for the rapid synaptic transmission that is critical for neuron-to-neuron communication, glutamate plays important role in neuronal growth and axon guidance, brain development and maturation, as well as synaptic plasticity in health and disease. Among the ionotropic and metabotropic glutamate receptors in the adult central nervous system, the N-methyl-D-aspartate (NMDA) type of glutamate receptor (NMDAR) acts as a hub by detecting and processing extracellular glutamate signals into diverse intracellular signaling outputs.
With the emergence of cellular and molecular biology, scientists are unraveling the mechanisms by which glutamate-mediated activation of the NMDAR in health and disease, transmits so many different functional outputs at both the microscopic neuron level and the macroscopic behavior level. These mechanisms have important implications for research concerning excitotoxicity and its role in ischemic neuronal death. The identification of distinct intracellular pathways linking NMDAR activation to neuronal death allows scientists to develop novel treatments that target specific death signaling pathways without affecting all the signaling pathways downstream of the receptor. This increased specificity not only translates into reduced side effects but also increases the therapeutic window in which the drug can be efficaciously administered. In this context, excitotoxicity in vitro models provide great facilitation for neuroscience research.
Fig.1 Expression pattern of glutamate receptors and transporters in brain cells. (Iovino, 2020)
Stress Granule Formation In Vitro Models
Stress granules are eukaryotic ribonucleoprotein (RNP) granules induced by various stresses that repress mRNA translation. These structures have been identified in the plant, yeast, and mammalian cells, and have been characterized microscopically by electron microscopy and immunofluorescence approaches.
Fig.2 Stress-specific proteomic. (Advani, 2020)
As ongoing research tries to decipher the cause of fatal neurodegenerative diseases, evidence of the involvement of stress granules is appearing. In Amyotrophic lateral sclerosis (ALS), the defected motor neurons, characterized by protein aggregates that emerge in the cytoplasm, lose their function and end up with motion paralysis. However, the molecular mechanism that leads to ALS is still missing. Most evidence points to prion-like domains, a common feature of RNA-binding proteins, as a key factor in this pathogenesis. The aggregation of TAR DNA-binding protein 43 (TDP-43) proteins alters the cell's response to stress by two pathways: i) disrupting mRNA sorting in the cells, required for proper processing and decay, due to massive fibrillary aggregates; ii) causing stress granules persistence even after stress resolution. Stress granule formation in vitro models will greatly contribute to clarifying the mechanism behind and accelerating ALS research.
Services at Creative Biolabs
Lesion induced cellular models are of great research significance in neuroscience. Based on our comprehensive neuroscience platform, Creative Biolabs provides customized lesion induced cellular models including NMDA lesion and glutamate lesion. We are devoted to accelerating neuroscience research by providing high-quality services.
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- Iovino, L.; et al. Glutamate-induced excitotoxicity in Parkinson's disease: The role of glial cells. J Pharmacol Sci. 2020, 144(3): 151-164.
- Advani, V. M., and Ivanov, P. Stress granule subtypes: an emerging link to neurodegeneration. Cell Mol Life Sci. 2020, 77(23): 4827-4845.