In the brain, we have about 100 billion of neurons but they represent only 10 to 50% of the total cells (von Bartheld et al., 2016). Indeed, glial cells, including astrocytes, oligodendrocytes and microglia are also essential to the physiological functions of the brain.
Parkinson’s Disease (PD) is the secondary common neurodegenerative disorder known after Alzheimer’s disease. Dopaminergic neurons in the substantia nigra pars compacta are the most affected from this cerebral pathology. This neuronal death is accompanied by a neuroinflammation, in which both microglia and astrocytes are greatly involved. In a certain way, chronic release of pro-inflammatory cytokines by microglia and astrocytes lead to the death of dopaminergic neurons. Consequently, if these cells are not regulated, they could promote the progression of PD.
In 2015, Wang et al. has summarized progresses in the neuroimmune aspects of PD. They approached that microglia have two alternative activation phenotypes: M1 (pro-inflammatory) phenotype and M2 (anti-inflammatory) phenotype, that could be characterized by secretion of different arrays of cytokines (Pisanu et al. 2014). Moreover, astrocytes can also be activated by a variety of molecules in pathological conditions. Indeed, reactive astrogliosis, which is characterized by high expression of glial fibrillary acid-protein (GFAP) in astrocytes, have been reported in PD animal models. This activation amplify the immune response. A synergy is created by the activation of both type of cells and enhanced the death of dopaminergic neurons (Saijo et al. 2009).
With the aim of giving cells a relevant environment for neuronal models for drug discovery in PD, we have realized a co-culture of dopaminergic neuronal cells (Luhmes cell line) and astrocytes (Human primary cells) in 2D and in 3D in BIOMIMESYS® Brain, our hyaluronic acid based hydroscaffold which mimics the extracellular matrix.
If you want to know more about our technology, please don’t hesitate to contact us!
von Bartheld, C.S., Bahney, J., and Herculano-Houzel, S. (2016). The Search for True Numbers of Neurons and Glial Cells in the Human Brain: A Review of 150 Years of Cell Counting. J Comp Neurol 524, 3865–3895.
Pisanu, A., Lecca, D., Mulas, G., Wardas, J., Simbula, G., Spiga, S., and Carta, A.R. (2014). Dynamic changes in pro- and anti-inflammatory cytokines in microglia after PPAR-γ agonist neuroprotective treatment in the MPTPp mouse model of progressive Parkinson’s disease. Neurobiol Dis 71, 280–291.
Saijo, K., Winner, B., Carson, C.T., Collier, J.G., Boyer, L., Rosenfeld, M.G., Gage, F.H., and Glass, C.K. (2009). A Nurr1/CoREST pathway in microglia and astrocytes protects dopaminergic neurons from inflammation-induced death. Cell 137, 47–59.
Wang, Q., Liu, Y., and Zhou, J. (2015). Neuroinflammation in Parkinson’s disease and its potential as therapeutic target. Transl Neurodegener 4, 19.