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Calcineurin A beta deficiency ameliorates HFD-induced hypothalamic astrocytosis in mice

Pfuhlmann, Katrin, Schriever, Sonja C., Legutko, Beata, Baumann, Peter, Harrison, Luke, Kabra, Dhiraj G., Baumgart, Emily Violette, Tschöp, Matthias H., Garcia-Caceres, Cristina, Pfluger, Paul T.·2018·Journal of Neuroinflammation
DOI 10.1186/s12974-018-1076-xPMC PMC5806488
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Fig. 1 Body weight, body composition, and blood glucose of WT and Pppcb KO mice. Subgroups of WT and Ppp3cb KO mice matched for body weight (a), fat mass (b), lean mass (c), and blood glucose levels after 5 h of fasting (d) were selected from a larger cohort of WT and Ppp3cb KO mice that were exposed to HFD for 16 weeks. The selected Ppp3cb KO mice nevertheless showed a decreased body weight gain over the period of HFD feeding when compared to their selected WT controls (e). n = 6. Means ± SEM. Student’s t test: *p < 0.05
Fig. 1 Body weight, body composition, and blood glucose of WT and Pppcb KO mice. Subgroups of WT and Ppp3cb KO mice matched for body weight (a), fat mass (b), lean mass (c), and blood glucose levels after 5 h of fasting (d) were selected from a larger cohort of WT and Ppp3cb KO mice that were exposed to HFD for 16 weeks. The selected Ppp3cb KO mice nevertheless showed a decreased body weight gain over the period of HFD feeding when compared to their selected WT controls (e). n = 6. Means ± SEM. Student’s t test: *p < 0.05CC BY · PubMed Central
Fig. 2 Ppp3cb deficiency is associated with a decrease in GFAP-positive cells in the ARC, DMH, and VMH of HFD-fed mice. Immunohistochemical stainings for GFAP in the arcuate nucleus (ARC), dorsomedial hypothalamus (DMH), and ventromedial hypothalamus (VMH) of HFD-fed Ppp3cb WT and KO mice. Representative images of the mediobasal hypothalamus (a, b, upper pictures) and of astrocytes in the ARC, VMH, DMH (a, b, lower pictures) of HFD-fed Ppp3cb WT, and KO mice. Numbers of GFAP-positive cells in the ARC (c), VMH (d), and DMH (e). Length of primary projections in the ARC of Ppp3cb WT and KO mice (f). Numbers of primary projection per astrocyte in the ARC (g), VMH (h), and DMH (i). Means ± SEM; n = 6 biological replicates per genotype (four pictures per biological replicate were quantified) except for (d), where only five KO brains could be used and (f) where length could be measured only in four KO brains; unpaired two-tailed Student’s t test. *p < 0.05, **p < 0.01
Fig. 2 Ppp3cb deficiency is associated with a decrease in GFAP-positive cells in the ARC, DMH, and VMH of HFD-fed mice. Immunohistochemical stainings for GFAP in the arcuate nucleus (ARC), dorsomedial hypothalamus (DMH), and ventromedial hypothalamus (VMH) of HFD-fed Ppp3cb WT and KO mice. Representative images of the mediobasal hypothalamus (a, b, upper pictures) and of astrocytes in the ARC, VMH, DMH (a, b, lower pictures) of HFD-fed Ppp3cb WT, and KO mice. Numbers of GFAP-positive cells in the ARC (c), VMH (d), and DMH (e). Length of primary projections in the ARC of Ppp3cb WT and KO mice (f). Numbers of primary projection per astrocyte in the ARC (g), VMH (h), and DMH (i). Means ± SEM; n = 6 biological replicates per genotype (four pictures per biological replicate were quantified) except for (d), where only five KO brains could be used and (f) where length could be measured only in four KO brains; unpaired two-tailed Student’s t test. *p < 0.05, **p < 0.01CC BY · PubMed Central
Fig. 3 Ppp3cb deficiency decreases the number of Iba1 positive cells in the VMH of HFD-fed mice. Immunohistochemical staining for Iba1 in the ARC, DMH, and VMH of Ppp3cb WT (a) and KO (b) mice and quantitative analysis of Iba1-positive microglia (c–e) in the ARC (c), VMH (d), and DMH (e). Means ± SEM; n = 6 WT and five KO mice (c), n = 6 mice per genotype (d, e); n = 4 pictures per biological replicate were quantified. Unpaired two-tailed Student’s t test. **p < 0.01
Fig. 3 Ppp3cb deficiency decreases the number of Iba1 positive cells in the VMH of HFD-fed mice. Immunohistochemical staining for Iba1 in the ARC, DMH, and VMH of Ppp3cb WT (a) and KO (b) mice and quantitative analysis of Iba1-positive microglia (c–e) in the ARC (c), VMH (d), and DMH (e). Means ± SEM; n = 6 WT and five KO mice (c), n = 6 mice per genotype (d, e); n = 4 pictures per biological replicate were quantified. Unpaired two-tailed Student’s t test. **p < 0.01CC BY · PubMed Central
Fig. 4 Pharmacological inhibition of calcineurin decreases GFAP fluorescence intensity in the ARC of mice acutely exposed to HFD. WT mice on chow (a, b) and HFD (c, d) were treated with 1 mg/kg/day of calcineurin inhibitor Fk506 for 1 week; HFD feeding was started in parallel. Fk506 treatment resulted in a significant reduction in body weight in mice on chow (a) and HFD (c), while no significant changes in body composition on chow (b) and HFD (d) were detected. GFAP (e, f) and IBA1 (g, h) staining in the ARC, VMH, and DMH of vehicle and Fk506-treated WT mice on HFD (scale 200 μm) revealed a decrease in GFAP fluorescence intensity in the ARC (e, f) Real-time qPCRs of mice on chow and HFD (i–m) were performed for Gfap and Iba1 (i), inflammatory cytokines (j), Cd169 as marker for monocyte infiltration (k), calcineurin subunits (l), and calcineurin downstream targets (m). Means ± SEM; n = 6 biological replicates (a, b); n = 10 biological replicates, except for lean mass vehicle, where one value was identified as a significant outlier (c, d); n = 4 biological replicates (f, g); n = 6 biological replicates, except for Gfap chow vehicle, where one value was identified as a significant outlier (i–m)
Fig. 4 Pharmacological inhibition of calcineurin decreases GFAP fluorescence intensity in the ARC of mice acutely exposed to HFD. WT mice on chow (a, b) and HFD (c, d) were treated with 1 mg/kg/day of calcineurin inhibitor Fk506 for 1 week; HFD feeding was started in parallel. Fk506 treatment resulted in a significant reduction in body weight in mice on chow (a) and HFD (c), while no significant changes in body composition on chow (b) and HFD (d) were detected. GFAP (e, f) and IBA1 (g, h) staining in the ARC, VMH, and DMH of vehicle and Fk506-treated WT mice on HFD (scale 200 μm) revealed a decrease in GFAP fluorescence intensity in the ARC (e, f) Real-time qPCRs of mice on chow and HFD (i–m) were performed for Gfap and Iba1 (i), inflammatory cytokines (j), Cd169 as marker for monocyte infiltration (k), calcineurin subunits (l), and calcineurin downstream targets (m). Means ± SEM; n = 6 biological replicates (a, b); n = 10 biological replicates, except for lean mass vehicle, where one value was identified as a significant outlier (c, d); n = 4 biological replicates (f, g); n = 6 biological replicates, except for Gfap chow vehicle, where one value was identified as a significant outlier (i–m)CC BY · PubMed Central

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Research works printed but not linked: 38

  1. Wilhelm I, Nyul-Toth A, Suciu M, Hermenean A, Krizbai IA. Heterogeneity of the blood-brain barrier. Tissue Barriers. 2016;4(1):e1143544. · DOI
  2. Garcia-Caceres C, Quarta C, Varela L, Gao Y, Gruber T, Legutko B, Jastroch M, Johansson P, Ninkovic J, Yi CX, et al. Astrocytic insulin signaling couples brain glucose uptake with nutrient availability. Cell. 2016;166(4):867–80. · DOI
  3. Halassa MM, Fellin T, Takano H, Dong JH, Haydon PG. Synaptic islands defined by the territory of a single astrocyte. J Neurosci. 2007;27(24):6473–7. · DOI · Paper page
  4. Haydon PG, Blendy J, Moss SJ, Rob Jackson F. Astrocytic control of synaptic transmission and plasticity: a target for drugs of abuse? Neuropharmacology. 2009;56(Suppl 1):83–90. · DOI
  5. Pekny M, Nilsson M. Astrocyte activation and reactive gliosis. Glia. 2005;50(4):427–34. · DOI · Paper page
  6. Canellada A, Ramirez BG, Minami T, Redondo JM, Cano E. Calcium/calcineurin signaling in primary cortical astrocyte cultures: Rcan1-4 and cyclooxygenase-2 as NFAT target genes. Glia. 2008;56(7):709–22. · DOI
  7. Sofroniew MV. Molecular dissection of reactive astrogliosis and glial scar formation. Trends Neurosci. 2009;32(12):638–47. · DOI · Paper page
  8. Thaler JP, Yi CX, Schur EA, Guyenet SJ, Hwang BH, Dietrich MO, Zhao X, Sarruf DA, Izgur V, Maravilla KR, et al. Obesity is associated with hypothalamic injury in rodents and humans. J Clin Invest. 2012;122(1):153–62. · DOI · Paper page
  9. Fuente-Martin E, Garcia-Caceres C, Granado M, de Ceballos ML, Sanchez-Garrido MA, Sarman B, Liu ZW, Dietrich MO, Tena-Sempere M, Argente-Arizon P, et al. Leptin regulates glutamate and glucose transporters in hypothalamic astrocytes. J Clin Invest. 2012;122(11):3900–13. · DOI
  10. De Souza CT, Araujo EP, Bordin S, Ashimine R, Zollner RL, Boschero AC, Saad MJ, Velloso LA. Consumption of a fat-rich diet activates a proinflammatory response and induces insulin resistance in the hypothalamus. Endocrinology. 2005;146(10):4192–9. · DOI · Paper page
  11. Zhang X, Zhang G, Zhang H, Karin M, Bai H, Cai D. Hypothalamic IKKbeta/NF-kappaB and ER stress link overnutrition to energy imbalance and obesity. Cell. 2008;135(1):61–73. · DOI · Paper page
  12. Milanski M, Degasperi G, Coope A, Morari J, Denis R, Cintra DE, Tsukumo DM, Anhe G, Amaral ME, Takahashi HK, et al. Saturated fatty acids produce an inflammatory response predominantly through the activation of TLR4 signaling in hypothalamus: implications for the pathogenesis of obesity. J Neurosci. 2009;29(2):359–70. · DOI · Paper page
  13. Gao Y, Ottaway N, Schriever SC, Legutko B, Garcia-Caceres C, de la Fuente E, Mergen C, Bour S, Thaler JP, Seeley RJ, et al. Hormones and diet, but not body weight, control hypothalamic microglial activity. Glia. 2014;62(1):17–25. · DOI
  14. Morari J, Anhe GF, Nascimento LF, de Moura RF, Razolli D, Solon C, Guadagnini D, Souza G, Mattos AH, Tobar N, et al. Fractalkine (CX3CL1) is involved in the early activation of hypothalamic inflammation in experimental obesity. Diabetes. 2014;63(11):3770–84. · DOI
  15. Klee CB, Crouch TH, Krinks MH. Calcineurin: a calcium- and calmodulin-binding protein of the nervous system. Proc Natl Acad Sci U S A. 1979;76(12):6270–3. · DOI · Paper page
  16. Pons S, Torres-Aleman I. Insulin-like growth factor-I stimulates dephosphorylation of ikappa B through the serine phosphatase calcineurin (protein phosphatase 2B). J Biol Chem. 2000;275(49):38620–5. · DOI
  17. Fernandez AM, Fernandez S, Carrero P, Garcia-Garcia M, Torres-Aleman I. Calcineurin in reactive astrocytes plays a key role in the interplay between proinflammatory and anti-inflammatory signals. J Neurosci. 2007;27(33):8745–56. · DOI · Paper page
  18. Norris CM, Kadish I, Blalock EM, Chen KC, Thibault V, Porter NM, Landfield PW, Kraner SD. Calcineurin triggers reactive/inflammatory processes in astrocytes and is upregulated in aging and Alzheimer's models. J Neurosci. 2005;25(18):4649–58. · DOI · Paper page
  19. Pfluger PT, Kabra DG, Aichler M, Schriever SC, Pfuhlmann K, Garcia VC, Lehti M, Weber J, Kutschke M, Rozman J, et al. Calcineurin links mitochondrial elongation with energy metabolism. Cell Metab. 2015;22(5):838–50. · DOI
  20. Bueno OF, Brandt EB, Rothenberg ME, Molkentin JD. Defective T cell development and function in calcineurin a beta -deficient mice. Proc Natl Acad Sci U S A. 2002;99(14):9398–403. · DOI
  21. Bueno OF, Wilkins BJ, Tymitz KM, Glascock BJ, Kimball TF, Lorenz JN, Molkentin JD. Impaired cardiac hypertrophic response in Calcineurin A beta-deficient mice. Proc Natl Acad Sci U S A. 2002;99(7):4586–91. · DOI
  22. Muzumdar MD, Tasic B, Miyamichi K, Li L, Luo L. A global double-fluorescent Cre reporter mouse. Genesis. 2007;45(9):593–605. · DOI · Paper page
  23. Gao L, Brenner D, Llorens-Bobadilla E, Saiz-Castro G, Frank T, Wieghofer P, Hill O, Thiemann M, Karray S, Prinz M, et al. Infiltration of circulating myeloid cells through CD95L contributes to neurodegeneration in mice. J Exp Med. 2015;212(4):469–80. · DOI · Paper page
  24. Furman JL, Sama DM, Gant JC, Beckett TL, Murphy MP, Bachstetter AD, Van Eldik LJ, Norris CM. Targeting astrocytes ameliorates neurologic changes in a mouse model of Alzheimer’s disease. J Neurosci. 2012;32(46):16129–40. · DOI · Paper page
  25. Serrano-Perez MC, Martin ED, Vaquero CF, Azcoitia I, Calvo S, Cano E, Tranque P. Response of transcription factor NFATc3 to excitotoxic and traumatic brain insults: identification of a subpopulation of reactive astrocytes. Glia. 2011;59(1):94–107. · DOI
  26. Sama MA, Mathis DM, Furman JL, Abdul HM, Artiushin IA, Kraner SD, Norris CM. Interleukin-1beta-dependent signaling between astrocytes and neurons depends critically on astrocytic calcineurin/NFAT activity. J Biol Chem. 2008;283(32):21953–64. · DOI
  27. Garcia-Caceres C, Fuente-Martin E, Burgos-Ramos E, Granado M, Frago LM, Barrios V, Horvath T, Argente J, Chowen JA. Differential acute and chronic effects of leptin on hypothalamic astrocyte morphology and synaptic protein levels. Endocrinology. 2011;152(5):1809–18. · DOI
  28. Pleiss MM, Sompol P, Kraner SD, Abdul HM, Furman JL, Guttmann RP, Wilcock DM, Nelson PT, Norris CM. Calcineurin proteolysis in astrocytes: implications for impaired synaptic function. Biochim Biophys Acta. 2016;1862(9):1521–32. · DOI
  29. Fernandez AM, Jimenez S, Mecha M, Davila D, Guaza C, Vitorica J, Torres-Aleman I. Regulation of the phosphatase calcineurin by insulin-like growth factor I unveils a key role of astrocytes in Alzheimer's pathology. Mol Psychiatry. 2012;17(7):705–18. · DOI
  30. Fernandez AM, Hervas R, Dominguez-Fraile M, Garrido VN, Gomez-Gutierrez P, Vega M, Vitorica J, Perez JJ, Torres Aleman I. Blockade of the interaction of Calcineurin with FOXO in Astrocytes protects against amyloid-beta-induced neuronal death. J Alzheimers Dis. 2016;52(4):1471–8. · DOI
  31. Furman JL, Sompol P, Kraner SD, Pleiss MM, Putman EJ, Dunkerson J, Mohmmad Abdul H, Roberts KN, Scheff SW, Norris CM. Blockade of astrocytic calcineurin/NFAT signaling helps to normalize Hippocampal synaptic function and plasticity in a rat model of traumatic brain injury. J Neurosci. 2016;36(5):1502–15. · DOI
  32. Chen Y, Holstein DM, Aime S, Bollo M, Lechleiter JD. Calcineurin beta protects brain after injury by activating the unfolded protein response. Neurobiol Dis. 2016;94:139–56. · DOI
  33. Matsuda T, Takuma K, Asano S, Kishida Y, Nakamura H, Mori K, Maeda S, Baba A. Involvement of calcineurin in Ca2+ paradox-like injury of cultured rat astrocytes. J Neurochem. 1998;70(5):2004–11. · DOI
  34. Pyrzynska B, Lis A, Mosieniak G, Kaminska B. Cyclosporin A-sensitive signaling pathway involving calcineurin regulates survival of reactive astrocytes. Neurochem Int. 2001;38(5):409–15. · DOI
  35. Gabryel B, Chalimoniuk M, Stolecka A, Waniek K, Langfort J, Malecki A. Inhibition of arachidonic acid release by cytosolic phospholipase A2 is involved in the antiapoptotic effect of FK506 and cyclosporin a on astrocytes exposed to simulated ischemia in vitro. J Pharmacol Sci. 2006;102(1):77–87. · DOI
  36. Gabryel B, Pudelko A, Adamczyk J, Fischer I, Malecki A. Calcineurin and Erk1/2-signaling pathways are involved in the antiapoptotic effect of cyclosporin a on astrocytes exposed to simulated ischemia in vitro. Naunyn Schmiedeberg's Arch Pharmacol. 2006;374(2):127–39. · DOI
  37. Szydlowska K, Zawadzka M, Kaminska B. Neuroprotectant FK506 inhibits glutamate-induced apoptosis of astrocytes in vitro and in vivo. J Neurochem. 2006;99(3):965–75. · DOI
  38. Furman JL, Artiushin IA, Norris CM. Disparate effects of serum on basal and evoked NFAT activity in primary astrocyte cultures. Neurosci Lett. 2010;469(3):365–9. · DOI

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Metadata

Authors
Pfuhlmann, K., Schriever, S. C., Legutko, B., Baumann, P., Harrison, L., Kabra, D. G., Baumgart, E. V., Tschöp, M. H., Garcia-Caceres, C., & Pfluger, P. T.
Venue
Journal of Neuroinflammation
Publisher
Springer Science and Business Media LLC
Published
2018-02-08
Volume
15
Issue
1
ISSN
1742-2094
DOI
10.1186/s12974-018-1076-x
PMC
PMC5806488
Cited by
9
References
3
Language
en
Funders
  • Helmholtz-Gemeinschaft (Portfolio Program Metabolic Dysfunction, ICEMED 'Imaging and Curing Environmental Metabolic Diseases' Alliance, Helmholtz-Israel-Cooperation in Personalized Medicine, Personalized Medicine Initiative, Initiative and Networking Fund)
  • Alexander von Humboldt-Stiftung

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CoChat. (2026). Citation check: Calcineurin A beta deficiency ameliorates HFD-induced hypothalamic astrocytosis in mice. https://app.cochat.ai/papers/10.1186/s12974-018-1076-x
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Pfuhlmann, K., Schriever, S. C., Legutko, B., Baumann, P., Harrison, L., Kabra, D. G., Baumgart, E. V., Tschöp, M. H., Garcia-Caceres, C., & Pfluger, P. T. (2018). Calcineurin A beta deficiency ameliorates HFD-induced hypothalamic astrocytosis in mice. Journal of Neuroinflammation. https://doi.org/10.1186/s12974-018-1076-x