Neuroinflammation

Inflammatory processes play a critical role in almost all neurological disorders. These processes may perhaps not trigger the disease, but derailed inflammatory processes certainly play a critical role in progression of the disease and ultimately brain dysfunction. Inflammatory responses therefore have diagnostic value, are important as biomarkers of therapeutic efficiency and provide an opportunity to modify the progression of neurological disorders. Not surprisingly, inflammatory responses in the brain have received a great deal of attention. Rodent models play an indispensable role studies into the complex interaction between the peripheral immune system and the brain. Several models of neurological diseases are instrumental in these studies.

Inflammasome

Several models available at Sylics are relevant in studies investigating effects on neuroinflammation. The acute MPTP-induced neurodegeneration model mimics dopaminergic cell loss as seen in Parkinson’s disease. Activation of the NLRP3 inflammasome in microglia plays a central role in dopaminergic neurodegeneration (see here).  Furthermore, in the mdx mouse model of Duchene Muscular Dystrophy available at Sylics, disease progression is significantly modified by interventions targeting the NLRP3 inflammasome activation (see here).

Microglia

Transgenic APP/PS1 mice express mutations in APP and PS1 proteins that lead to early onset Alzheimer’s disease in humans. These mice show typical Abeta plaques in the cortex from the age of approximately 6 months onwards (see reference images). Besides Abeta plaques, typical hallmarks of neuroinflammation are seen in the brains of these mice. Microglia are the brains resident macrophages. These cells account for 10-15% of the cells in the brain and are normally small and distributed in a well-ordered fashion with numerous ramifications (see control wild-type mice). In the brains of APP/PS1 mice microglia show a reactive phenotype, characterized by a swollen cell body and retracted ramifications (Iba1 antibody).

Astrocytes

Astrocytes are star shaped cells that provide essential support to neurons and synapses. Most astrocytes express GFAP at low levels under healthy conditions. Upon response to triggers in their proximity, reactive astrocytes upregulate GFAP leading to an increased number of GFAP cells. This increase in GFAP reactivity is seen in plaque bearing APP/PS1 mice in comparison with control wild type mice.

Besides the makers mentioned on this page, Sylics runs several immunohistochemical stainings routinely. Please reach out to us if you want to learn more about neuroinflammatory processes in the models described above, and how this may be relevant to your drug-discovery project.