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A comparative review of cell culture systems for the study of microglial biology in Alzheimer’s disease
Open accessAbstract
Over the past two decades, it has become increasingly apparent that Alzheimer’s disease neuropathology is characterized by activated microglia (brain resident macrophages) as well as the classic features of amyloid plaques and neurofibrillary tangles. The intricacy of microglial biology has also become apparent, leading to a heightened research interest in this particular cell type. Over the years a number of different microglial cell culturing techniques have been developed to study either primary mammalian microglia, or immortalized cell lines. Each microglial system has advantages and disadvantages and should be selected for its appropriateness in a particular research context. This review summarizes several of the most common microglial cell culture systems currently being employed in Alzheimer’s research including primary microglia; BV2 and N9 retroviral immortalized microglia; human immortalized microglia (HMO6); and spontaneously immortalized rodent microglial lines (EOC lines and HAPI cells). Particularities of cell culture requirements and characteristics of microglial behavior, especially in response to applied inflammogen stimuli, are compared and discussed across these cell types.
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“However, several reports have indicated that differences between immortalized cell lines and primary murine microglia are not insignificant [83,84].”
From Lipoprotein Lipase Regulates Microglial Lipid Droplet Accumulation (2021) · cites this paper as [84]
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Cites
Localization of the glial fibrillary acidic protein in astrocytes by immunofluorescence
Bignami, A., Eng, L. F., Dahl, D. R., & Uyeda, C. T. (1972) · Brain Research · doi:10.1016/0006-8993(72)90398-8 · Cited by 1,456
Microglial Dysfunction and Defective β-Amyloid Clearance Pathways in Aging Alzheimer's Disease Mice
Hickman, S. E., Allison, E. K., & El Khoury, J. (2008) · The Journal of Neuroscience · doi:10.1523/jneurosci.0616-08.2008 · Cited by 1,329
Characterization of ameboid microglia isolated from developing mammalian brain
Giulian, D., & Baker, T. J. (1986) · Journal of Neuroscience · doi:10.1523/jneurosci.06-08-02163.1986 · Cited by 1,300
Immortalization of murine microglial cells by a v-raf / v-myc carrying retrovirus
Blasi, E., Barluzzi, R., Bocchini, V., Mazzolla, R., & Bistoni, F. (1990) · Journal of Neuroimmunology · doi:10.1016/0165-5728(90)90073-v · Cited by 1,076
Cytology & cellular pathology of the nervous system
Penfield, W. G. (1965) · Medical Entomology and Zoology · Cited by 1,035
Microglial-produced nitric oxide and reactive nitrogen oxides mediate neuronal cell death
Boje, K. M., & Arora, P. K. (1992) · Brain Research · doi:10.1016/0006-8993(92)91004-x · Cited by 944
Production of superoxide anions by a CNS macrophage, the microglia
Colton, C. A., & Gilbert, D. L. (1987) · FEBS Letters · doi:10.1016/0014-5793(87)80305-8 · Cited by 614
Li, Y., Liu, L., Barger, S. W., & Griffin, W. S. T. (2003) · The Journal of Neuroscience · doi:10.1523/jneurosci.23-05-01605.2003 · Cited by 563
Koenigsknecht-Talboo, J., & Landreth, G. E. (2005) · The Journal of Neuroscience · doi:10.1523/jneurosci.1808-05.2005 · Cited by 477
The origin and cell lineage of microglia: new concepts
Chan, W. Y., Kohsaka, S., & Rezaie, P. (2007) · Brain Research Reviews · doi:10.1016/j.brainresrev.2006.11.002 · Cited by 400 · cited 1×
“These findings support the idea that there is heterogeneity of the microglial cell origins in the CNS, with one population from myeloid/ mesenchymal origin (not necessarily derived from monocytes) and a second population representing a developmental and transitory form of fetal macrophage (possibly monocyte), which is…”
Monokine production by microglial cell clones
Righi, M., Mori, L., Libero, G. D., Sironi, M., Biondi, A., Mantovani, A., Donini, S. D., & Ricciardi‐Castagnoli, P. (1989) · European Journal of Immunology · doi:10.1002/eji.1830190815 · Cited by 368
Microglia in ALS: The Good, The Bad, and The Resting
Henkel, J. S., Beers, D. R., Zhao, W., & Appel, S. H. (2009) · Journal of Neuroimmune Pharmacology · doi:10.1007/s11481-009-9171-5 · Cited by 353
Mouse microglial cells express a plasma membrane pore gated by extracellular ATP
Ferrari, D., Villalba, M., Chiozzi, P., Falzoni, S., Ricciardi‐Castagnoli, P., & Virgilio, F. D. (1996) · The Journal of Immunology · doi:10.4049/jimmunol.156.4.1531 · Cited by 352
Novel anti-inflammatory therapy for Parkinson's disease
Gao, H., Liu, B., Zhang, W., & Hong, J. (2003) · Trends in Pharmacological Sciences · doi:10.1016/s0165-6147(03)00176-7 · Cited by 325
Maezawa, I., Zimin, P. I., Wulff, H., & Jin, L. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.135244 · Cited by 293
Horvath, R. J., Nutile‐McMenemy, N., Alkaitis, M. S., & DeLeo, J. A. (2008) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2008.05633.x · Cited by 264
Blasi, E., Mathieson, B. J., Varesio, L., Cleveland, J. L., Borchert, P., & Rapp, U. R. (1985) · Nature · doi:10.1038/318667a0 · Cited by 248
Hensley, K. (2003) · Neurobiology of Disease · doi:10.1016/s0969-9961(03)00087-1 · Cited by 229
Self-citationCytology and Cellular Pathology of the Nervous System
G., J. G. (1933) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp.s1-13.51.273-a · Cited by 220
Induction of serine racemase expression and D-serine release from microglia by amyloid beta-peptide.
Wu, S., Bodles, A. M., Porter, M. M., Griffin, W. S. T., Basile, A. S., & Barger, S. W. (2004) · Journal of Neuroinflammation · doi:10.1186/1742-2094-1-2 · Cited by 189
Fu, H., Liu, B., Frost, J. L., Hong, S., Jin, M., Ostaszewski, B., Shankar, G. M., Costantino, I. M., Carroll, M. C., Mayadas, T. N., et al. (2012) · Glia · doi:10.1002/glia.22331 · Cited by 180
Zhao, W., Xie, W., Xiao, Q., Beers, D. R., & Appel, S. H. (2006) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2006.04172.x · Cited by 176
Takata, K., Kitamura, Y., Saeki, M., Terada, M., Kagitani, S., Kitamura, R., Fujikawa, Y., Maelicke, A., Tomimoto, H., Taniguchi, T., et al. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.142356 · Cited by 176
Characterization of a novel brain‐derived microglial cell line isolated from neonatal rat brain
Cheepsunthorn, P., Radov, L. A., Menzies, S. L., Reid, J., & Connor, J. R. (2001) · Glia · doi:10.1002/glia.1070 · Cited by 163
β-Amyloid protein-dependent nitric oxide production from microglial cells and neurotoxicity
Ii, M., Sunamoto, M., Ohnishi, K., & Ichimori, Y. (1996) · Brain Research · doi:10.1016/0006-8993(96)00156-4 · Cited by 163
Human CD34 + cells differentiate into microglia and express recombinant therapeutic protein
Asheuer, M., Pflumio, F., Benhamida, S., Dubart‐Kupperschmitt, A., Fouquet, F., Imai, Y., Aubourg, P. R., & Cartier, N. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0306431101 · Cited by 163
Nagai, A., Nakagawa, E., Hatori, K., Choi, H. B., McLarnon, J. G., Lee, M. A., & Kim, S. U. (2001) · Neurobiology of Disease · doi:10.1006/nbdi.2001.0437 · Cited by 156
Microglia and the Immune Pathology of Alzheimer Disease
Giulian, D. (1999) · The American Journal of Human Genetics · doi:10.1086/302477 · Cited by 141
West, M. S., Mhatre, M., Ceballos, A., Floyd, R. A., Grammas, P., Gabbita, S. P., Hamdheydari, L., Mai, T., Mou, S., Pye, Q. N., et al. (2004) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2004.02700.x · Cited by 121
Self-citationAlzheimer's β‐Amyloid Peptide 1–42 Induces a Phagocytic Response in Murine Microglia
Kopec, K. K., & Carroll, R. T. (1998) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.1998.71052123.x · Cited by 102
Tocharus, J., Khonthun, C., Chongthammakun, S., & Govitrapong, P. (2010) · Journal of Pineal Research · doi:10.1111/j.1600-079x.2010.00761.x · Cited by 102
Walker, W. S., Gatewood, J., Olivas, E., Askew, D., & Havenith, C. E. G. (1995) · Journal of Neuroimmunology · doi:10.1016/0165-5728(95)00146-8 · Cited by 91
Human Microglial Cells Synthesize Albumin in BrainPreprint
Ahn, S., Byun, K., Cho, K., Kim, J. Y., Yoo, J. S., Kim, D., Paek, S. H., Kim, S. U., Simpson, R. J., & Lee, B. (2008) · Nature Precedings · doi:10.1371/journal.pone.0002829 · Cited by 87
Distinct modulation of microglial amyloid β phagocytosis and migration by neuropeptidesi
Fleisher‐Berkovich, S., Filipovich‐Rimon, T., Ben-Shmuel, S., Hülsmann, C., Kummer, M. P., & Heneka, M. T. (2010) · Journal of Neuroinflammation · doi:10.1186/1742-2094-7-61 · Cited by 82
Hensley, K., Christov, A., Kamat, S., Zhang, X. C., Jackson, K. W., Snow, S., & Post, J. (2010) · Journal of Neuroscience · doi:10.1523/jneurosci.5247-09.2010 · Cited by 78
Self-citationHe, F. Q., Qiu, B. Y., Li, T., Xie, Q., Cui, D. J., Huang, X. L., & Gan, H. T. (2011) · International Immunopharmacology · doi:10.1016/j.intimp.2011.03.023 · Cited by 58
Microglia in the Human Nervous System during Development
Rezaie, P. (2003) · Neuroembryology and Aging · doi:10.1159/000068498 · Cited by 38
Rezaie, P., & Male, D. (2002) · Neuroembryology and Aging · doi:10.1159/000051020 · Cited by 34
β-adaptin: Key molecule for microglial scavenger receptor function under oxidative stress
Manzano-León, N., Delgado-Coello, B., Guaderrama-Díaz, M., & Mas-Oliva, J. (2006) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2006.10.077 · Cited by 14
Research works printed but not linked: 1
- Castero J: Estudie del compotemento de la microglia cultivade on vetro. Datos concernientes a su histogenesis. Mem R Soc Cep Hist Nat 1930, 14:125–182.
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Doench, J. G., Fusi, N., Sullender, M., Hegde, M., Vaimberg, E. W., Donovan, K. F., Smith, I., Tothova, Z., Wilen, C., Orchard, R., et al. (2016) · Nature Biotechnology · doi:10.1038/nbt.3437 · Cited by 4,637
TREM2 mutations implicated in neurodegeneration impair cell surface transport and phagocytosis
Kleinberger, G., Yamanishi, Y., Suárez-Calvet, M., Czirr, E., Lohmann, E., Cuyvers, E., Struyfs, H., Pettkus, N., Wenninger-Weinzierl, A., Mazaheri, F., et al. (2014) · Science Translational Medicine · doi:10.1126/scitranslmed.3009093 · Cited by 798
Bohlen, C. J., Bennett, F. C., Tucker, A. F., Collins, H. Y., Mulinyawe, S. B., & Barres, B. A. (2017) · Neuron · doi:10.1016/j.neuron.2017.04.043 · Cited by 658
Alternatively activated microglia and macrophages in the central nervous system
Franco, R., & Fernández‐Suárez, D. (2015) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2015.05.003 · Cited by 674
Microglia amplify inflammatory activation of astrocytes in manganese neurotoxicity
Kirkley, K. S., Popichak, K. A., Afzali, M. F., Legare, M. E., & Tjalkens, R. B. (2017) · Journal of Neuroinflammation · doi:10.1186/s12974-017-0871-0 · Cited by 331
Metadata
- Authors
- Stansley, B., Post, J., & Hensley, K.
- Affiliations
- University of Toledo Medical Center (US)
- Corresponding author
- Hensley, Kenneth
- ORCID
- Stansley, Branden
- Venue
- Journal of Neuroinflammation
- Published
- 2012-05-31
- Volume
- 9
- Issue
- 1
- Pages
- 115-115
- ISSN
- 1742-2094 (ISSN-L)
- PMC
- PMC3407712
- OpenAlex
- W2164594351
- Cited by
- 419
- References
- 40
- Citations by year
- 2026: 29 · 2025: 27 · 2024: 27 · 2023: 32 · 2022: 49 · 2021: 46 · 2020: 42 · 2019: 30 · 2018: 25 · 2017: 32 · 2016: 29 · 2015: 16 · 2014: 21 · 2013: 12 · 2012: 2
- FWCI
- 8.22
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Journal of Neuroinflammation (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- National Institutes of Health (5r21ns066279-03)
- National Institute on Aging (R01AG031553)
- National Institute on Drug Abuse (DA7606, R01DA007606)
- National Institute of Neurological Disorders and Stroke (R21-NS066279)
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Neurological Disease Mechanisms and Treatments
- Keywords
- microglia, Alzheimer's disease, primary microglia, BV-2 cells, N9 cells, microglial activation, neuroinflammation, amyloid plaques, neurofibrillary tangles
- MeSH terms
- Alzheimer Disease, Animals, Cell Line, Transformed, Cells, Cultured, Humans, Microglia, Cell Culture Techniques
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