Non-Neuronal Cells Are Required to Mediate the Effects of Neuroinflammation: Results from a Neuron-Enriched Culture System

PloS One
Chin Wai HuiKarl Herrup

Abstract

Chronic inflammation is associated with activated microglia and reactive astrocytes and plays an important role in the pathogenesis of neurodegenerative diseases such as Alzheimer's. Both in vivo and in vitro studies have demonstrated that inflammatory cytokine responses to immune challenges contribute to neuronal death during neurodegeneration. In order to investigate the role of glial cells in this phenomenon, we developed a modified method to remove the non-neuronal cells in primary cultures of E16.5 mouse cortex. We modified previously reported methods as we found that a brief treatment with the thymidine analog, 5-fluorodeoxyuridine (FdU), is sufficient to substantially deplete dividing non-neuronal cells in primary cultures. Cell cycle and glial markers confirm the loss of ~99% of all microglia, astrocytes and oligodendrocyte precursor cells (OPCs). More importantly, under this milder treatment, the neurons suffered neither cell loss nor any morphological defects up to 2.5 weeks later; both pre- and post-synaptic markers were retained. Further, neurons in FdU-treated cultures remained responsive to excitotoxicity induced by glutamate application. The immunobiology of the FdU culture, however, was significantly changed. Co...Continue Reading

References

Mar 18, 1997·Proceedings of the National Academy of Sciences of the United States of America·B KaltschmidtC Kaltschmidt
Feb 13, 2001·The Journal of Clinical Investigation·M P Mattson, S Camandola
Mar 26, 2003·Cell Death and Differentiation·H WajantP Scheurich
May 22, 2003·The Journal of Immunology : Official Journal of the American Association of Immunologists·Fan YangCun-Yu Wang
Jun 3, 2004·Neurobiology of Aging·Robert G NageleJarek Wegiel
Jul 2, 2004·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Bénédicte Salthun-LassallePatrick P Michel
Jan 18, 2005·Trends in Biochemical Sciences·Patrick ViatourAlain Chariot
Aug 18, 2005·The Journal of Biological Chemistry·Carl Y SasakiDan L Longo
Sep 30, 2005·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Masashi KitazawaFrank M LaFerla
Mar 30, 2006·Journal of Neuroinflammation·Clive BateAlun Williams
Dec 6, 2008·Cell Death and Differentiation·J J RodríguezA Verkhratsky
Apr 23, 2009·Neuroscience Letters·Lakshmi ThirumangalakudiPaula Grammas
Oct 14, 2009·Neurobiology of Disease·Vien Nguyen, Patrick S McQuillen
Nov 13, 2009·The Journal of Clinical Investigation·Nicholas H VarvelKarl Herrup
Jan 13, 2010·Cold Spring Harbor Perspectives in Biology·Andrea Oeckinghaus, Sankar Ghosh
Jan 22, 2010·Journal of Neuroscience Research·Deanna L TaylorHuseyin Mehmet
Jun 12, 2010·Human Molecular Genetics·Joy IrobiVincent Timmerman
May 9, 2012·International Immunopharmacology·Heung-Soon LeeSang-Hyun Choi
May 9, 2012·PloS One·Eric J HillH Rheinallt Parri
Mar 28, 2013·Frontiers in Neurology·Diana G Hernandez-OntiverosCesar V Borlongan
Aug 13, 2013·Molecular and Cellular Neurosciences·Berta HenriquezBrigitte van Zundert
Mar 21, 2015·Lancet Neurology·Michael T HenekaMarkus P Kummer

❮ Previous
Next ❯

Citations

Nov 20, 2016·The Journal of Histochemistry and Cytochemistry : Official Journal of the Histochemistry Society·Michelle H TheusXin M Luo
Nov 8, 2018·Journal of Neuroinflammation·Chin Wai HuiKarl Herrup
Jul 13, 2018·Frontiers in Neuroscience·Peter VerstraelenWinnok H De Vos
Oct 29, 2019·Journal of Neural Engineering·Lorenzo MuzziJoost le Feber
May 13, 2019·Medical & Biological Engineering & Computing·Jude Pj SavarrajMark A DeCoster
Nov 15, 2020·Trends in Neurosciences·Bindu D PaulVilhelm A Bohr
Jan 29, 2021·Expert Review of Neurotherapeutics·Peter JennerRobert A Hauser
Apr 20, 2018·Bio-protocol·Luana Naia, A Cristina Rego
Jul 31, 2021·Frontiers in Cellular Neuroscience·Elnaz KhezerlouMark A DeCoster
Aug 23, 2021·The Ocular Surface·Sonja MertschStefan Schrader
Apr 20, 2018··Ana Cristina RegoLuana  Naia

❮ Previous
Next ❯

Methods Mentioned

BETA
Protein Assay
electrophoresis
PCR

Software Mentioned

Prism
GraphPad
ImageJ

Related Concepts

Related Feeds

Alzheimer's Disease: Microglia

Microglia are a type of glial cell found throughout the brain and spinal cord. Microglia have been found to be associated with Alzheimer's disease development and progression. Here are the latest discoveries pertaining to Alzheimer's disease and microglia.

Alzheimer's Disease: Amyloid Beta

Alzheimer's disease is a neurodegenerative disease associated with the accumulation of amyloid plaques in the brain; these plaques are comprised of amyloid beta deposits. Here is the latest research in this field.

Alzheimer's Disease: APP

Amyloid precursor protein (APP) proteolysis is critical for the development of Alzheimer's disease, a neurodegenerative disease associated with accumulation of amyloid plaques in the brain. Here is the latest research on APP and Alzheimer's disease.

Astrocytes & Amyloid

Astrocytes are thought to play a role in amyloid production and have been implicated in neurodegenerative diseases such as Alzheimer’s disease. Here is the latest research on the relationship between astrocytes and amyloid.

Astrocytes

Astrocytes are glial cells that support the blood-brain barrier, facilitate neurotransmission, provide nutrients to neurons, and help repair damaged nervous tissues. Here is the latest research.

Astrocytes & Neurodegeneration

Astrocytes are important for the health and function of the central nervous system. When these cells stop functioning properly, either through gain of function or loss of homeostatic controls, neurodegenerative diseases can occur. Here is the latest research on astrocytes and neurodegeneration.

Related Papers

Frontiers in Molecular Neuroscience
Nataša Kopitar-Jerala
Neurological Sciences : Official Journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology
Hironori YokoyamaTsutomu Araki
Critical Reviews in Oral Biology and Medicine : an Official Publication of the American Association of Oral Biologists
S R Barnum
© 2022 Meta ULC. All rights reserved