Metabolic and inflammatory adaptation of reactive astrocytes: role of PPARs
Abstract
Astrocyte-mediated inflammation is associated with degenerative pathologies such as Alzheimer's and Parkinson's diseases and multiple sclerosis. The acute inflammation and morphological and metabolic changes that astrocytes develop after the insult are known as reactive astroglia or astrogliosis that is an important response to protect and repair the lesion. Astrocytes optimize their metabolism to produce lactate, glutamate, and ketone bodies in order to provide energy to the neurons that are deprived of nutrients upon insult. Firstly, we review the basis of inflammation and morphological changes of the different cell population implicated in reactive gliosis. Next, we discuss the more active metabolic pathways in healthy astrocytes and explain the metabolic response of astrocytes to the insult in different pathologies and which metabolic alterations generate complications in these diseases. We emphasize the role of peroxisome proliferator-activated receptors isotypes in the inflammatory and metabolic adaptation of astrogliosis developed in ischemia or neurodegenerative diseases. Based on results reported in astrocytes and other cells, we resume and hypothesize the effect of peroxisome proliferator-activated receptor (PPAR) activation with ligands on different metabolic pathways in order to supply energy to the neurons. The activation of selective PPAR isotype activity may serve as an input to better understand the role played by these receptors on the metabolic and inflammat…
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In astrocytes, about 60% of pyruvate is converted into lactate by lactate dehydrogenase, which restricts the amount of pyruvate oxidized within mitochondria.
“in astrocytes, ~60% pyruvate is converted into lactate by the lactate dehydrogenase, which restricts the amount of pyruvate oxidized within mitochondria (Iglesias et al., 2017).”
From Inhibition of the mitochondrial pyruvate carrier in astrocytes reduces amyloid and tau accumulation in the 3xTgAD mouse model of Alzheimer's disease (2024) · cites this paper as Iglesias et al., 2017
Cites
Cahoy, J. D., Emery, B., Kaushal, A., Foo, L. C., Zamanian, J. L., Christopherson, K. S., Xing, Y., Lubischer, J. L., Krieg, P. A., Krupenko, S. A., et al. (2008) · The Journal of Neuroscience · doi:10.1523/jneurosci.4178-07.2008 · Cited by 3,129 · see citing works
Heterogeneity in the distribution and morphology of microglia in the normal adult mouse brain
Lawson, L. J., Perry, V. H., Dri, P., & Gordon, S. (1990) · Neuroscience · doi:10.1016/0306-4522(90)90229-w · Cited by 2,045 · see citing works
Astrocyte-Neuron Lactate Transport Is Required for Long-Term Memory Formation
Suzuki, A., Stern, S. A., Bozdagi, O., Huntley, G. W., Walker, R. H., Magistretti, P. J., & Alberini, C. M. (2011) · Cell · doi:10.1016/j.cell.2011.02.018 · Cited by 1,711 · see citing works
Middeldorp, J., & Hol, E. M. (2011) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2011.01.005 · Cited by 1,080 · see citing works
Wanner, I. B., Anderson, M. A., Song, B., Levine, J., Fernandez, A., Gray-Thompson, Z., Ao, Y., & Sofroniew, M. V. (2013) · Journal of Neuroscience · doi:10.1523/jneurosci.2121-13.2013 · Cited by 839 · see citing works
Wilhelmsson, U., Li, L., Pekna, M., Berthold, C.-H., Blom, S., Eliasson, C., Renner, O., Bushong, E., Ellisman, M., Morgan, T. E., et al. (2004) · The Journal of Neuroscience · doi:10.1523/jneurosci.0820-04.2004 · Cited by 455 · see citing works
Mandrekar-Colucci, S., Karlo, J. C., & Landreth, G. E. (2012) · The Journal of Neuroscience · doi:10.1523/jneurosci.5268-11.2012 · Cited by 355 · see citing works
Chuquet, J., Quilichini, P., Nimchinsky, E. A., & Buzsáki, G. (2010) · The Journal of Neuroscience · doi:10.1523/jneurosci.0762-10.2010 · Cited by 217 · see citing works
Molecular targets of non-steroidal anti-inflammatory drugs in neurodegenerative diseases
Lleo, A., Galea, E., & Sastre, M. (2007) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-007-6516-1 · Cited by 93 · see citing works
Joiner, T. E., Lewinsohn, P. M., & Seeley, J. R. (2002) · Journal of Personality Assessment · doi:10.1207/s15327752jpa7903_05 · Cited by 87 · see citing works
Why does the brain (not) have glycogen?
DiNuzzo, M., Maraviglia, B., & Giove, F. (2011) · BioEssays · doi:10.1002/bies.201000151 · Cited by 53 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Regulation of Ketone Body Metabolism and the Role of PPARα
Grabacka, M., Pierzchalska, M., Dean, M., & Reiss, K. (2016) · International Journal of Molecular Sciences · doi:10.3390/ijms17122093 · Cited by 305 · see citing works
Ali, S. S., Al-Tohamy, R., Al-Zahrani, M., Schagerl, M., Kornaros, M., & Sun, J. (2025) · Microbial Cell Factories · doi:10.1186/s12934-025-02685-1 · Cited by 88 · see citing works
Adlimoghaddam, A., Odero, G. G., Glazner, G., Turner, R. S., & Albensi, B. C. (2021) · Aging and disease · doi:10.14336/ad.2020.0910 · Cited by 38 · see citing works
Ceyzériat, K., Badina, A. M., Petrelli, F., Montessuit, S., Nicolaides, A., Millet, P., Savioz, A., Martinou, J.-C., & Tournier, B. B. (2024) · Neurobiology of Disease · doi:10.1016/j.nbd.2024.106623 · Cited by 18 · see citing works
- Authors
- Iglesias, J., Morales, L., & Barreto, G. E.
- Affiliations
- Pontificia Universidad Javeriana (CO)
- Corresponding author
- Iglesias, José
- Venue
- Molecular Neurobiology
- Published
- 2016-03-17
- Volume
- 54
- Issue
- 4
- Pages
- 2518-2538
- ISSN
- 0893-7648 (ISSN-L)
- 1559-1182
- OpenAlex
- W2297591945
- Cited by
- 137
- References
- 11
- Citations by year
- 2026: 5 · 2025: 13 · 2024: 9 · 2023: 14 · 2022: 10 · 2021: 21 · 2020: 15 · 2019: 13 · 2018: 16 · 2017: 14 · 2016: 7
- FWCI
- 1.45
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Molecular Neurobiology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Pontificia Universidad Javeriana
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- reactive astrocytes, astrocyte activation, astrocyte metabolism, peroxisome proliferator-activated receptors, neuroinflammation, lactic acid production, ketone bodies, glutamate, ischemia, neurodegenerative diseases, traumatic brain injury, PPAR ligands, neuroprotection
- MeSH terms
- Animals, Astrocytes, Gliosis, Humans, Inflammation, Models, Biological, Peroxisome Proliferator-Activated Receptors
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
