Glial Dysfunction in MeCP2 Deficiency Models: Implications for Rett Syndrome
Abstract
:1. Introduction
2. Astrocytes in Rett Syndrome
2.1. Differences in Gene Expression
2.2. Irregular Shape and Maturation
2.3. Dysfunction in Metabolic Support
2.4. Dysfunction of Potassium and Neurotransmitter Homeostasis
2.5. Astrocyte Reactivity and Rett Syndrome
2.6. Dysfunction of Astrocytic Support to Synaptogenesis and Dendritic Morphology
2.7. Gliotransmission
2.8. Contribution of RTT Astrocytes to the Breathing Phenomenon
3. Microglia in Rett Syndrome
4. Oligodendrocytes and OPC in Rett Syndrome
5. Developmental Aspects of Glial Dysfunction in Rett Syndrome
6. Conclusions
Conflicts of Interest
References
- Ehinger, Y.; Matagne, V.; Villard, L.; Roux, J.C. Rett syndrome from bench to bedside: Recent advances. F1000Research 2018, 7, 398. [Google Scholar] [CrossRef] [PubMed]
- Liyanage, V.R.; Rastegar, M. Rett syndrome and MeCP2. Neuromol. Med. 2014, 16, 231–264. [Google Scholar] [CrossRef] [PubMed]
- Amir, R.E.; Van den Veyver, I.B.; Wan, M.; Tran, C.Q.; Francke, U.; Zoghbi, H.Y. Rett syndrome is caused by mutations in X-linked MECP2, encoding methyl-CpG-binding protein 2. Nat. Genet. 1999, 23, 185–188. [Google Scholar] [CrossRef] [PubMed]
- Neul, J.L.; Benke, T.A.; Marsh, E.D.; Skinner, S.A.; Merritt, J.; Lieberman, D.N.; Standridge, S.; Feyma, T.; Heydemann, P.; Peters, S.; et al. The array of clinical phenotypes of males with mutations in Methyl-CpG binding protein 2. Am. J. Med. Genet. B Neuropsychiatr. Genet. 2019, 180, 55–67. [Google Scholar] [CrossRef] [PubMed]
- Ross, P.D.; Guy, J.; Selfridge, J.; Kamal, B.; Bahey, N.; Tanner, K.E.; Gillingwater, T.H.; Jones, R.A.; Loughrey, C.M.; McCarroll, C.S.; et al. Exclusive expression of MeCP2 in the nervous system distinguishes between brain and peripheral Rett syndrome-like phenotypes. Hum. Mol. Genet. 2016, 25, 4389–4404. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Shahbazian, M.D.; Antalffy, B.; Armstrong, D.L.; Zoghbi, H.Y. Insight into Rett syndrome: MeCP2 levels display tissue-and cell-specific differences and correlate with neuronal maturation. Hum. Mol. Genet. 2002, 11, 115–124. [Google Scholar] [CrossRef] [PubMed]
- Aber, K.M.; Nori, P.; MacDonald, S.M.; Bibat, G.; Jarrar, M.H.; Kaufmann, W.E. Methyl-CpG-binding protein 2 is localized in the postsynaptic compartment: An immunochemical study of subcellular fractions. Neuroscience 2003, 116, 77–80. [Google Scholar] [CrossRef]
- Akbarian, S.; Chen, R.Z.; Gribnau, J.; Rasmussen, T.P.; Fong, H.; Jaenisch, R.; Jones, E.G. Expression pattern of the Rett syndrome gene MeCP2 in primate prefrontal cortex. Neurobiol. Dis. 2001, 8, 784–791. [Google Scholar] [CrossRef] [PubMed]
- Kishi, N.; Macklis, J.D. MECP2 is progressively expressed in post-migratory neurons and is involved in neuronal maturation rather than cell fate decisions. Mol. Cell. Neurosci. 2004, 27, 306–321. [Google Scholar] [CrossRef] [PubMed]
- Jung, B.P.; Jugloff, D.G.; Zhang, G.; Logan, R.; Brown, S.; Eubanks, J.H. The expression of methyl CpG binding factor MeCP2 correlates with cellular differentiation in the developing rat brain and in cultured cells. J. Neurobiol. 2003, 55, 86–96. [Google Scholar] [CrossRef]
- Colantuoni, C.; Jeon, O.H.; Hyder, K.; Chenchik, A.; Khimani, A.H.; Narayanan, V.; Hoffman, E.P.; Kaufmann, W.E.; Naidu, S.; Pevsner, J. Gene expression profiling in postmortem rett syndrome brain: Differential gene expression and patient classification. Neurobiol. Dis. 2001, 8, 847–865. [Google Scholar] [CrossRef] [PubMed]
- Nagai, K.; Miyake, K.; Kubota, T. A transcriptional repressor MeCP2 causing Rett syndrome is expressed in embryonic non-neuronal cells and controls their growth. Dev. Brain Res. 2005, 157, 103–106. [Google Scholar] [CrossRef] [PubMed]
- Ballas, N.; Lioy, D.T.; Grunseich, C.; Mandel, G. Non-cell autonomous influence of MeCP2-deficient glia on neuronal dendritic morphology. Nat. Neurosci. 2009, 12, 311–317. [Google Scholar] [CrossRef] [PubMed]
- Kifayathullah, L.A.; Arunachalam, J.P.; Bodda, C.; Agbemenyah, H.Y.; Laccone, F.A.; Mannan, A.U. MeCP2270 mutant protein is expressed in astrocytes as well as in neurons and localizes in the nucleus. Cytogenet. Genome Res. 2010, 129, 290–297. [Google Scholar] [CrossRef] [PubMed]
- Maezawa, I.; Swanberg, S.; Harvey, D.; LaSalle, J.M.; Jin, L.W. Rett syndrome astrocytes are abnormal and spread MeCP2 deficiency through gap junctions. J. Neurosci. 2009, 29, 5051–5061. [Google Scholar] [CrossRef] [PubMed]
- Molofsky, A.V.; Krencik, R.; Ullian, E.M.; Tsai, H.H.; Deneen, B.; Richardson, W.D.; Barres, B.A.; Rowitch, D.H. Astrocytes and disease: A neurodevelopmental perspective. Genes Dev. 2012, 26, 891–907. [Google Scholar] [CrossRef] [PubMed]
- Zhang, Y.; Chen, K.; Sloan, S.A.; Bennett, M.L.; Scholze, A.R.; O’Keeffe, S.; Phatnani, H.P.; Guarnieri, P.; Caneda, C.; Ruderisch, N.; et al. An RNA-sequencing transcriptome and splicing database of glia, neurons, and vascular cells of the cerebral cortex. J. Neurosci. 2014, 34, 11929–11947. [Google Scholar] [CrossRef] [PubMed]
- Alvarez-Saavedra, M.; Saez, M.A.; Kang, D.; Zoghbi, H.Y.; Young, J.I. Cell-specific expression of wild-type MeCP2 in mouse models of Rett syndrome yields insight about pathogenesis. Hum. Mol. Genet. 2007, 16, 2315–2325. [Google Scholar] [CrossRef]
- Robertson, J.M. Astrocyte domains and the three-dimensional and seamless expression of consciousness and explicit memories. Med. Hypotheses 2013, 81, 1017–1024. [Google Scholar] [CrossRef]
- Barres, B.A. The mystery and magic of glia: A perspective on their roles in health and disease. Neuron 2008, 60, 430–440. [Google Scholar] [CrossRef]
- Okabe, Y.; Takahashi, T.; Mitsumasu, C.; Kosai, K.; Tanaka, E.; Matsuishi, T. Alterations of gene expression and glutamate clearance in astrocytes derived from an MeCP2-null mouse model of Rett syndrome. PLoS ONE 2012, 7, e35354. [Google Scholar] [CrossRef] [PubMed]
- Yasui, D.H.; Xu, H.; Dunaway, K.W.; Lasalle, J.M.; Jin, L.W.; Maezawa, I. MeCP2 modulates gene expression pathways in astrocytes. Mol. Autism 2013, 4, 3. [Google Scholar] [CrossRef] [PubMed]
- Delepine, C.; Nectoux, J.; Letourneur, F.; Baud, V.; Chelly, J.; Billuart, P.; Bienvenu, T. Astrocyte transcriptome from the Mecp2(308)-Truncated mouse model of rett syndrome. Neuromol. Med. 2015, 17, 353–363. [Google Scholar] [CrossRef] [PubMed]
- Lange, S.C.; Bak, L.K.; Waagepetersen, H.S.; Schousboe, A.; Norenberg, M.D. Primary cultures of astrocytes: Their value in understanding astrocytes in health and disease. Neurochem. Res. 2012, 37, 2569–2588. [Google Scholar] [CrossRef] [PubMed]
- Pacheco, N.L.; Heaven, M.R.; Holt, L.M.; Crossman, D.K.; Boggio, K.J.; Shaffer, S.A.; Flint, D.L.; Olsen, M.L. RNA sequencing and proteomics approaches reveal novel deficits in the cortex of Mecp2-deficient mice, a model for Rett syndrome. Mol. Autism 2017, 8, 56. [Google Scholar] [CrossRef] [PubMed]
- Forbes-Lorman, R.M.; Kurian, J.R.; Auger, A.P. MeCP2 regulates GFAP expression within the developing brain. Brain Res. 2014, 1543, 151–158. [Google Scholar] [CrossRef] [PubMed]
- Montgomery, K.R.; Louis Sam Titus, A.S.C.; Wang, L.; D’Mello, S.R. Elevated MeCP2 in mice causes neurodegeneration involving tau dysregulation and excitotoxicity: Implications for the understanding and treatment of MECP2 triplication syndrome. Mol. Neurobiol. 2018, 55, 9057–9074. [Google Scholar] [CrossRef]
- Yang, Y.; Higashimori, H.; Morel, L. Developmental maturation of astrocytes and pathogenesis of neurodevelopmental disorders. J. Neurodev. Disords 2013, 5, 22. [Google Scholar] [CrossRef]
- Schiweck, J.; Eickholt, B.J.; Murk, K. Important shapeshifter: mechanisms allowing astrocytes to respond to the changing nervous system during development, injury and disease. Front. Cell. Neurosci. 2018, 12, 261. [Google Scholar] [CrossRef]
- Yasui, T.; Uezono, N.; Nakashima, H.; Noguchi, H.; Matsuda, T.; Noda-Andoh, T.; Okano, H.; Nakashima, K. Hypoxia Epigenetically confers astrocytic differentiation potential on human pluripotent cell-derived neural precursor cells. Stem Cell Rep. 2017, 8, 1743–1756. [Google Scholar] [CrossRef]
- De Filippis, B.; Fabbri, A.; Simone, D.; Canese, R.; Ricceri, L.; Malchiodi-Albedi, F.; Laviola, G.; Fiorentini, C. Modulation of RhoGTPases improves the behavioral phenotype and reverses astrocytic deficits in a mouse model of Rett syndrome. Neuropsychopharmacology 2012, 37, 1152–1163. [Google Scholar] [CrossRef] [PubMed]
- Nguyen, M.V.; Du, F.; Felice, C.A.; Shan, X.; Nigam, A.; Mandel, G.; Robinson, J.K.; Ballas, N. MeCP2 is critical for maintaining mature neuronal networks and global brain anatomy during late stages of postnatal brain development and in the mature adult brain. J. Neurosci. 2012, 32, 10021–10034. [Google Scholar] [CrossRef] [PubMed]
- Nectoux, J.; Florian, C.; Delepine, C.; Bahi-Buisson, N.; Khelfaoui, M.; Reibel, S.; Chelly, J.; Bienvenu, T. Altered microtubule dynamics in Mecp2-deficient astrocytes. J. Neurosci. Res. 2012, 90, 990–998. [Google Scholar] [CrossRef] [PubMed]
- Delepine, C.; Meziane, H.; Nectoux, J.; Opitz, M.; Smith, A.B.; Ballatore, C.; Saillour, Y.; Bennaceur-Griscelli, A.; Chang, Q.; Williams, E.C.; et al. Altered microtubule dynamics and vesicular transport in mouse and human MeCP2-deficient astrocytes. Hum. Mol. Genet. 2016, 25, 146–157. [Google Scholar] [CrossRef] [PubMed]
- Stobart, J.L.; Anderson, C.M. Multifunctional role of astrocytes as gatekeepers of neuronal energy supply. Front. Cell. Neurosci. 2013, 7, 38. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Saywell, V.; Viola, A.; Confort-Gouny, S.; Le Fur, Y.; Villard, L.; Cozzone, P.J. Brain magnetic resonance study of Mecp2 deletion effects on anatomy and metabolism. Biochem. Biophys. Res. Commun. 2006, 340, 776–783. [Google Scholar] [CrossRef] [PubMed]
- Li, Y.; Wang, H.; Muffat, J.; Cheng, A.W.; Orlando, D.A.; Loven, J.; Kwok, S.M.; Feldman, D.A.; Bateup, H.S.; Gao, Q.; et al. Global transcriptional and translational repression in human-embryonic-stem-cell-derived Rett syndrome neurons. Cell Stem Cell 2013, 13, 446–458. [Google Scholar] [CrossRef] [PubMed]
- Grosser, E.; Hirt, U.; Janc, O.A.; Menzfeld, C.; Fischer, M.; Kempkes, B.; Vogelgesang, S.; Manzke, T.U.; Opitz, L.; Salinas-Riester, G.; et al. Oxidative burden and mitochondrial dysfunction in a mouse model of Rett syndrome. Neurobiol. Dis. 2012, 48, 102–114. [Google Scholar] [CrossRef] [PubMed]
- Bebensee, D.F.; Can, K.; Muller, M. Increased mitochondrial mass and cytosolic redox imbalance in hippocampal astrocytes of a mouse model of rett syndrome: subcellular changes revealed by ratiometric imaging of JC-1 and roGFP1 fluorescence. Oxid. Med. Cell. Longev. 2017, 2017, 3064016. [Google Scholar] [CrossRef]
- Dave, A.; Shukla, F.; Wala, H.; Pillai, P. Mitochondrial electron transport chain complex dysfunction in MeCP2 Knock-Down astrocytes: Protective effects of quercetin hydrate. J. Mol. Neurosci. 2019, 67, 16–27. [Google Scholar] [CrossRef]
- Hardeland, R. Melatonin and the electron transport chain. Cell. Mol. Life Sci. 2017, 74, 3883–3896. [Google Scholar] [CrossRef] [PubMed]
- Magistretti, P.J.; Allaman, I. Lactate in the brain: From metabolic end-product to signalling molecule. Nat. Rev. Neurosci. 2018, 19, 235–249. [Google Scholar] [CrossRef] [PubMed]
- Nielsen, J.B.; Toft, P.B.; Reske-Nielsen, E.; Jensen, K.E.; Christiansen, P.; Thomsen, C.; Henriksen, O.; Lou, H.C. Cerebral magnetic resonance spectroscopy in Rett syndrome. Failure to detect mitochondrial disorder. Brain Dev. 1993, 15, 107–112. [Google Scholar] [CrossRef]
- Turovsky, E.; Karagiannis, A.; Abdala, A.P.; Gourine, A.V. Impaired CO2 sensitivity of astrocytes in a mouse model of Rett syndrome. J. Physiol. 2015, 593, 3159–3168. [Google Scholar] [CrossRef] [PubMed]
- Sofroniew, M.V.; Vinters, H.V. Astrocytes: Biology and pathology. Acta Neuropathol. 2010, 119, 7–35. [Google Scholar] [CrossRef] [PubMed]
- Mahmoud, S.; Gharagozloo, M.; Simard, C.; Gris, D. Astrocytes maintain glutamate homeostasis in the cns by controlling the balance between glutamate uptake and release. Cells 2019, 8, 184. [Google Scholar] [CrossRef] [PubMed]
- Lappalainen, R.; Riikonen, R.S. High levels of cerebrospinal fluid glutamate in Rett syndrome. Pediatr. Neurol. 1996, 15, 213–216. [Google Scholar] [CrossRef]
- Horska, A.; Farage, L.; Bibat, G.; Nagae, L.M.; Kaufmann, W.E.; Barker, P.B.; Naidu, S. Brain metabolism in Rett syndrome: Age, clinical, and genotype correlations. Ann. Neurol. 2009, 65, 90–97. [Google Scholar] [CrossRef]
- Bellot-Saez, A.; Kekesi, O.; Morley, J.W.; Buskila, Y. Astrocytic modulation of neuronal excitability through K+ spatial buffering. Neurosci. Biobehav. Rev. 2017, 77, 87–97. [Google Scholar] [CrossRef]
- Djukic, B.; Casper, K.B.; Philpot, B.D.; Chin, L.S.; McCarthy, K.D. Conditional knock-out of Kir4.1 leads to glial membrane depolarization, inhibition of potassium and glutamate uptake, and enhanced short-term synaptic potentiation. J. Neurosci. 2007, 27, 11354–11365. [Google Scholar] [CrossRef]
- Larson, V.A.; Mironova, Y.; Vanderpool, K.G.; Waisman, A.; Rash, J.E.; Agarwal, A.; Bergles, D.E. Oligodendrocytes control potassium accumulation in white matter and seizure susceptibility. eLife 2018, 7, e34829. [Google Scholar] [CrossRef] [PubMed]
- Nwaobi, S.E.; Lin, E.; Peramsetty, S.R.; Olsen, M.L. DNA methylation functions as a critical regulator of Kir4.1 expression during CNS development. Glia 2014, 62, 411–427. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Kahanovitch, U.; Cuddapah, V.A.; Pacheco, N.L.; Holt, L.M.; Mulkey, D.K.; Percy, A.K.; Olsen, M.L. MeCP2 Deficiency Leads to Loss of Glial Kir4.1. eNeuro 2018, 5. [Google Scholar] [CrossRef] [PubMed]
- Zhang, X.; Su, J.; Cui, N.; Gai, H.; Wu, Z.; Jiang, C. The disruption of central CO2 chemosensitivity in a mouse model of Rett syndrome. Am. J. Physiol. Cell Physiol. 2011, 301, C729–C738. [Google Scholar] [CrossRef] [PubMed]
- Pekny, M.; Pekna, M. Astrocyte reactivity and reactive astrogliosis: Costs and benefits. Physiol. Rev. 2014, 94, 1077–1098. [Google Scholar] [CrossRef] [PubMed]
- Samaco, R.C.; Neul, J.L. Complexities of Rett syndrome and MeCP2. J. Neurosci. 2011, 31, 7951–7959. [Google Scholar] [CrossRef] [PubMed]
- Jellinger, K.; Seitelberger, F. Neuropathology of Rett syndrome. Am. J. Med. Genet. Suppl. 1986, 1, 259–288. [Google Scholar] [CrossRef] [PubMed]
- Oldfors, A.; Hagberg, B.; Nordgren, H.; Sourander, P.; Witt-Engerstrom, I. Rett syndrome: Spinal cord neuropathology. Pediatr. Neurol. 1988, 4, 172–174. [Google Scholar] [CrossRef]
- Oldfors, A.; Sourander, P.; Armstrong, D.L.; Percy, A.K.; Witt-Engerstrom, I.; Hagberg, B.A. Rett syndrome: Cerebellar pathology. Pediatr. Neurol. 1990, 6, 310–314. [Google Scholar] [CrossRef]
- Lipani, J.D.; Bhattacharjee, M.B.; Corey, D.M.; Lee, D.A. Reduced nerve growth factor in Rett syndrome postmortem brain tissue. J. Neuropathol. Exp. Neurol. 2000, 59, 889–895. [Google Scholar] [CrossRef]
- Armstrong, D.D. Neuropathology of Rett syndrome. J. Child Neurol. 2005, 20, 747–753. [Google Scholar] [CrossRef]
- Deguchi, K.; Antalffy, B.A.; Twohill, L.J.; Chakraborty, S.; Glaze, D.G.; Armstrong, D.D. Substance P immunoreactivity in Rett syndrome. Pediatr. Neurol. 2000, 22, 259–266. [Google Scholar] [CrossRef]
- Andoh-Noda, T.; Akamatsu, W.; Miyake, K.; Matsumoto, T.; Yamaguchi, R.; Sanosaka, T.; Okada, Y.; Kobayashi, T.; Ohyama, M.; Nakashima, K.; et al. Differentiation of multipotent neural stem cells derived from Rett syndrome patients is biased toward the astrocytic lineage. Mol. Brain 2015, 8, 31. [Google Scholar] [CrossRef]
- Setoguchi, H.; Namihira, M.; Kohyama, J.; Asano, H.; Sanosaka, T.; Nakashima, K. Methyl-CpG binding proteins are involved in restricting differentiation plasticity in neurons. J. Neurosci. Res. 2006, 84, 969–979. [Google Scholar] [CrossRef]
- Sochocka, M.; Diniz, B.S.; Leszek, J. Inflammatory Response in the CNS: Friend or Foe? Mol. Neurobiol. 2017, 54, 8071–8089. [Google Scholar] [CrossRef]
- Nance, E.; Kambhampati, S.P.; Smith, E.S.; Zhang, Z.; Zhang, F.; Singh, S.; Johnston, M.V.; Kannan, R.M.; Blue, M.E.; Kannan, S. Dendrimer-mediated delivery of N-acetyl cysteine to microglia in a mouse model of Rett syndrome. J. Neuroinflamm. 2017, 14, 252. [Google Scholar] [CrossRef] [Green Version]
- Chung, W.S.; Allen, N.J.; Eroglu, C. Astrocytes Control Synapse Formation, Function, and Elimination. Cold Spring Harb. Perspect. Biol. 2015, 7, a020370. [Google Scholar] [CrossRef] [Green Version]
- Allen, N.J.; Eroglu, C. Cell Biology of Astrocyte-Synapse Interactions. Neuron 2017, 96, 697–708. [Google Scholar] [CrossRef]
- Williams, E.C.; Zhong, X.; Mohamed, A.; Li, R.; Liu, Y.; Dong, Q.; Ananiev, G.E.; Mok, J.C.; Lin, B.R.; Lu, J.; et al. Mutant astrocytes differentiated from Rett syndrome patients-specific iPSCs have adverse effects on wild-type neurons. Hum. Mol. Genet. 2014, 23, 2968–2980. [Google Scholar] [CrossRef]
- Buch, L.; Lipi, B.; Langhnoja, J.; Jaldeep, L.; Pillai, P.P.; Prakash, P. Role of astrocytic MeCP2 in regulation of CNS myelination by affecting oligodendrocyte and neuronal physiology and axo-glial interactions. Exp. Brain Res. 2018, 236, 3015–3027. [Google Scholar] [CrossRef]
- Lioy, D.T.; Garg, S.K.; Monaghan, C.E.; Raber, J.; Foust, K.D.; Kaspar, B.K.; Hirrlinger, P.G.; Kirchhoff, F.; Bissonnette, J.M.; Ballas, N.; et al. A role for glia in the progression of Rett’s syndrome. Nature 2011, 475, 497–500. [Google Scholar] [CrossRef]
- Maezawa, I.; Jin, L.W. Rett Syndrome Microglia Damage Dendrites and Synapses by the Elevated Release of Glutamate. J. Neurosci. 2010, 30, 5346–5356. [Google Scholar] [CrossRef] [Green Version]
- Holt, L.M.; Stoyanof, S.T.; Olsen, M.L. Magnetic Cell Sorting for In Vivo and In Vitro Astrocyte, Neuron, and Microglia Analysis. Curr. Protoc. Neurosci. 2019, 88, e71. [Google Scholar] [CrossRef]
- Domingues, H.S.; Portugal, C.C.; Socodato, R.; Relvas, J.B. Oligodendrocyte, Astrocyte, and Microglia Crosstalk in Myelin Development, Damage, and Repair. Front. Cell Dev. Biol. 2016, 4, 71. [Google Scholar]
- Araque, A.; Carmignoto, G.; Haydon, P.G.; Oliet, S.H.; Robitaille, R.; Volterra, A. Gliotransmitters travel in time and space. Neuron 2014, 81, 728–739. [Google Scholar] [CrossRef]
- Haydon, P.G.; Nedergaard, M. How do astrocytes participate in neural plasticity? Cold Spring Harb. Perspect. Biol. 2014, 7, a020438. [Google Scholar] [CrossRef]
- Fiacco, T.A.; McCarthy, K.D. Multiple Lines of Evidence Indicate That Gliotransmission Does Not Occur under Physiological Conditions. J. Neurosci. 2018, 38, 3–13. [Google Scholar] [CrossRef]
- Savtchouk, I.; Volterra, A. Gliotransmission: Beyond Black-and-White. J. Neurosci. 2018, 38, 14–25. [Google Scholar] [CrossRef]
- Rakela, B.; Brehm, P.; Mandel, G. Astrocytic modulation of excitatory synaptic signaling in a mouse model of Rett syndrome. eLife 2018, 7, e31629. [Google Scholar] [CrossRef]
- Dong, Q.; Liu, Q.; Li, R.; Wang, A.; Bu, Q.; Wang, K.H.; Chang, Q. Mechanism and consequence of abnormal calcium homeostasis in Rett syndrome astrocytes. eLife 2018, 7, e33417. [Google Scholar] [CrossRef]
- Funk, G.D.; Rajani, V.; Alvares, T.S.; Revill, A.L.; Zhang, Y.; Chu, N.Y.; Biancardi, V.; Linhares-Taxini, C.; Katzell, A.; Reklow, R. Neuroglia and their roles in central respiratory control; an overview. Comp. Biochem. Physiol. A Mol. Integr. Physiol. 2015, 186, 83–95. [Google Scholar] [CrossRef]
- Gourine, A.V.; Kasymov, V.; Marina, N.; Tang, F.; Figueiredo, M.F.; Lane, S.; Teschemacher, A.G.; Spyer, K.M.; Deisseroth, K.; Kasparov, S. Astrocytes control breathing through pH-dependent release of ATP. Science 2010, 329, 571–575. [Google Scholar] [CrossRef]
- Wenker, I.C.; Sobrinho, C.R.; Takakura, A.C.; Moreira, T.S.; Mulkey, D.K. Regulation of ventral surface CO2/H+-sensitive neurons by purinergic signalling. J. Physiol. 2012, 590, 2137–2150. [Google Scholar] [CrossRef]
- Wenker, I.C.; Kreneisz, O.; Nishiyama, A.; Mulkey, D.K. Astrocytes in the retrotrapezoid nucleus sense H+ by inhibition of a Kir4.1-Kir5.1-like current and may contribute to chemoreception by a purinergic mechanism. J. Neurophysiol. 2010, 104, 3042–3052. [Google Scholar] [CrossRef]
- James, S.D.; Hawkins, V.E.; Falquetto, B.; Ruskin, D.N.; Masino, S.A.; Moreira, T.S.; Olsen, M.L.; Mulkey, D.K. Adenosine Signaling through A1 Receptors Inhibits Chemosensitive Neurons in the Retrotrapezoid Nucleus. eNeuro 2018, 5. [Google Scholar] [CrossRef]
- Garg, S.K.; Lioy, D.T.; Knopp, S.J.; Bissonnette, J.M. Conditional depletion of methyl-CpG-binding protein 2 in astrocytes depresses the hypercapnic ventilatory response in mice. J. Appl. Physiol. (1985) 2015, 119, 670–676. [Google Scholar] [CrossRef] [Green Version]
- Li, W.; Pozzo-Miller, L. BDNF deregulation in Rett syndrome. Neuropharmacology 2014, 76, 737–746. [Google Scholar] [CrossRef]
- Chen, L.; Chen, K.; Lavery, L.A.; Baker, S.A.; Shaw, C.A.; Li, W.; Zoghbi, H.Y. MeCP2 binds to non-CG methylated DNA as neurons mature, influencing transcription and the timing of onset for Rett syndrome. Proc. Natl. Acad. Sci. USA 2015, 112, 5509–5514. [Google Scholar] [CrossRef] [Green Version]
- Abuhatzira, L.; Makedonski, K.; Kaufman, Y.; Razin, A.; Shemer, R. MeCP2 deficiency in the brain decreases BDNF levels by REST/CoREST-mediated repression and increases TRKB production. Epigenetics 2007, 2, 214–222. [Google Scholar] [CrossRef]
- Chang, Q.; Khare, G.; Dani, V.; Nelson, S.; Jaenisch, R. The disease progression of Mecp2 mutant mice is affected by the level of BDNF expression. Neuron 2006, 49, 341–348. [Google Scholar] [CrossRef]
- Poyhonen, S.; Er, S.; Domanskyi, A.; Airavaara, M. Effects of neurotrophic factors in glial cells in the central nervous system: expression and properties in neurodegeneration and injury. Front. Physiol. 2019, 10, 486. [Google Scholar] [CrossRef]
- Rousseaud, A.; Delepine, C.; Nectoux, J.; Billuart, P.; Bienvenu, T. Differential expression and regulation of Brain-Derived Neurotrophic Factor (BDNF) mRNA isoforms in brain cells from Mecp2(308/y) mouse model. J. Mol. Neurosci. 2015, 56, 758–767. [Google Scholar] [CrossRef]
- Caravagna, C.; Soliz, J.; Seaborn, T. Brain-derived neurotrophic factor interacts with astrocytes and neurons to control respiration. Eur. J. Neurosci. 2013, 38, 3261–3269. [Google Scholar] [CrossRef]
- Wolf, S.A.; Boddeke, H.W.; Kettenmann, H. Microglia in physiology and disease. Annu. Rev. Physiol. 2017, 79, 619–643. [Google Scholar] [CrossRef]
- Muffat, J.; Li, Y.; Yuan, B.; Mitalipova, M.; Omer, A.; Corcoran, S.; Bakiasi, G.; Tsai, L.H.; Aubourg, P.; Ransohoff, R.M.; et al. Efficient derivation of microglia-like cells from human pluripotent stem cells. Nat. Med. 2016, 22, 1358–1367. [Google Scholar] [CrossRef] [Green Version]
- Cronk, J.C.; Derecki, N.C.; Ji, E.; Xu, Y.; Lampano, A.E.; Smirnov, I.; Baker, W.; Norris, G.T.; Marin, I.; Coddington, N.; et al. Methyl-CpG binding protein 2 regulates microglia and macrophage gene expression in response to inflammatory stimuli. Immunity 2015, 42, 679–691. [Google Scholar] [CrossRef]
- Horiuchi, M.; Smith, L.; Maezawa, I.; Jin, L.W. CX3CR1 ablation ameliorates motor and respiratory dysfunctions and improves survival of a Rett syndrome mouse model. Brain Behav. Immun. 2017, 60, 106–116. [Google Scholar] [CrossRef]
- Smith, E.S.; Smith, D.R.; Eyring, C.; Braileanu, M.; Smith-Connor, K.S.; Ei Tan, Y.; Fowler, A.Y.; Hoffman, G.E.; Johnston, M.V.; Kannan, S.; et al. Altered trajectories of neurodevelopment and behavior in mouse models of Rett syndrome. Neurobiol. Learn. Mem. 2018. [Google Scholar] [CrossRef]
- Cronk, J.C.; Derecki, N.C.; Litvak, V.; Kipnis, J. Unexpected cellular players in Rett syndrome pathology. Neurobiol. Dis. 2016, 92, 64–71. [Google Scholar] [CrossRef]
- Diaz de Leon-Guerrero, S.; Pedraza-Alva, G.; Perez-Martinez, L. In sickness and in health: The role of methyl-CpG binding protein 2 in the central nervous system. Eur. J. Neurosci. 2011, 33, 1563–1574. [Google Scholar] [CrossRef]
- Zhao, D.; Mokhtari, R.; Pedrosa, E.; Birnbaum, R.; Zheng, D.; Lachman, H.M. Transcriptome analysis of microglia in a mouse model of Rett syndrome: Differential expression of genes associated with microglia/macrophage activation and cellular stress. Mol. Autism. 2017, 8, 17. [Google Scholar] [CrossRef]
- Nakagawa, Y.; Chiba, K. Diversity and plasticity of microglial cells in psychiatric and neurological disorders. Pharmacol. Ther. 2015, 154, 21–35. [Google Scholar] [CrossRef]
- Tropea, D.; Giacometti, E.; Wilson, N.R.; Beard, C.; McCurry, C.; Fu, D.D.; Flannery, R.; Jaenisch, R.; Sur, M. Partial reversal of Rett Syndrome-like symptoms in MeCP2 mutant mice. Proc. Natl. Acad. Sci. USA 2009, 106, 2029–2034. [Google Scholar] [CrossRef] [Green Version]
- Pini, G.; Congiu, L.; Benincasa, A.; DiMarco, P.; Bigoni, S.; Dyer, A.H.; Mortimer, N.; Della-Chiesa, A.; O’Leary, S.; McNamara, R.; et al. Illness severity, social and cognitive ability, and EEG analysis of ten patients with rett syndrome treated with mecasermin (Recombinant Human IGF-1). Autism. Res. Treat. 2016, 2016, 5073078. [Google Scholar] [CrossRef]
- Jin, L.W.; Horiuchi, M.; Wulff, H.; Liu, X.B.; Cortopassi, G.A.; Erickson, J.D.; Maezawa, I. Dysregulation of glutamine transporter SNAT1 in Rett syndrome microglia: A mechanism for mitochondrial dysfunction and neurotoxicity. J. Neurosci. 2015, 35, 2516–2529. [Google Scholar] [CrossRef]
- Maezawa, I.; Calafiore, M.; Wulff, H.; Jin, L.-W. Does microglial dysfunction play a role in autism and Rett syndrome? Neuron Glia Biol. 2011, 7, 85–97. [Google Scholar] [CrossRef] [Green Version]
- Derecki, N.C.; Cronk, J.C.; Lu, Z.; Xu, E.; Abbott, S.B.; Guyenet, P.G.; Kipnis, J. Wild-type microglia arrest pathology in a mouse model of Rett syndrome. Nature 2012, 484, 105–109. [Google Scholar] [CrossRef] [Green Version]
- Hughes, V. Microglia: The constant gardeners. Nature 2012, 485, 570–572. [Google Scholar] [CrossRef] [Green Version]
- Wang, J.; Wegener, J.E.; Huang, T.W.; Sripathy, S.; De Jesus-Cortes, H.; Xu, P.; Tran, S.; Knobbe, W.; Leko, V.; Britt, J.; et al. Wild-type microglia do not reverse pathology in mouse models of Rett syndrome. Nature 2015, 521, E1–E4. [Google Scholar] [CrossRef] [Green Version]
- Paolicelli, R.C.; Ferretti, M.T. Function and dysfunction of microglia during brain development: Consequences for synapses and neural circuits. Front. Synaptic Neurosci. 2017, 9, 9. [Google Scholar] [CrossRef]
- Schafer, D.P.; Heller, C.T.; Gunner, G.; Heller, M.; Gordon, C.; Hammond, T.; Wolf, Y.; Jung, S.; Stevens, B. Microglia contribute to circuit defects in Mecp2 null mice independent of microglia-specific loss of Mecp2 expression. eLife 2016, 5, e15224. [Google Scholar] [CrossRef]
- Parikh, Z.S.; Tripathi, A.; Pillai, P.P. Differential regulation of MeCP2 phosphorylation by laminin in oligodendrocytes. J. Mol. Neurosci. 2017, 62, 309–317. [Google Scholar] [CrossRef]
- Wakai, S.; Kameda, K.; Ishikawa, Y.; Miyamoto, S.; Nagaoka, M.; Okabe, M.; Minami, R.; Tachi, N. Rett syndrome: Findings suggesting axonopathy and mitochondrial abnormalities. Pediatr. Neurol. 1990, 6, 339–343. [Google Scholar] [CrossRef]
- Papadimitriou, J.M.; Hockey, A.; Tan, N.; Masters, C.L. Rett syndrome: Abnormal membrane-bound lamellated inclusions in neurons and oligodendroglia. Am. J. Med. Genet. 1988, 29, 365–368. [Google Scholar] [CrossRef]
- Nguyen, M.V.; Felice, C.A.; Du, F.; Covey, M.V.; Robinson, J.K.; Mandel, G.; Ballas, N. Oligodendrocyte lineage cells contribute unique features to Rett syndrome neuropathology. J. Neurosci. 2013, 33, 18764–18774. [Google Scholar] [CrossRef]
- Luikenhuis, S.; Giacometti, E.; Beard, C.F.; Jaenisch, R. Expression of MeCP2 in postmitotic neurons rescues Rett syndrome in mice. Proc. Natl. Acad. Sci. USA 2004, 101, 6033–6038. [Google Scholar] [CrossRef] [Green Version]
- Sharma, K.; Singh, J.; Pillai, P.P.; Frost, E.E. Involvement of MeCP2 in Regulation of Myelin-Related Gene Expression in Cultured Rat Oligodendrocytes. J. Mol. Neurosci. 2015, 57, 176–184. [Google Scholar] [CrossRef]
- Alessio, N.; Riccitiello, F.; Squillaro, T.; Capasso, S.; Del Gaudio, S.; Di Bernardo, G.; Cipollaro, M.; Melone, M.A.B.; Peluso, G.; Galderisi, U. Neural stem cells from a mouse model of Rett syndrome are prone to senescence, show reduced capacity to cope with genotoxic stress, and are impaired in the differentiation process. Exp. Mol. Med. 2018, 50, 1. [Google Scholar] [CrossRef] [Green Version]
- Tsujimura, K.; Abematsu, M.; Kohyama, J.; Namihira, M.; Nakashima, K. Neuronal differentiation of neural precursor cells is promoted by the methyl-CpG-binding protein MeCP2. Exp. Neurol. 2009, 219, 104–111. [Google Scholar] [CrossRef]
- Gao, H.; Bu, Y.; Wu, Q.; Wang, X.; Chang, N.; Lei, L.; Chen, S.; Liu, D.; Zhu, X.; Hu, K.; et al. Mecp2 regulates neural cell differentiation by suppressing the Id1 to Her2 axis in zebrafish. J. Cell Sci. 2015, 128, 2340–2350. [Google Scholar] [CrossRef] [Green Version]
- Okabe, Y.; Kusaga, A.; Takahashi, T.; Mitsumasu, C.; Murai, Y.; Tanaka, E.; Higashi, H.; Matsuishi, T.; Kosai, K. Neural development of methyl-CpG-binding protein 2 null embryonic stem cells: A system for studying Rett syndrome. Brain Res. 2010, 1360, 17–27. [Google Scholar] [CrossRef]
- Fan, G.; Martinowich, K.; Chin, M.H.; He, F.; Fouse, S.D.; Hutnick, L.; Hattori, D.; Ge, W.; Shen, Y.; Wu, H.; et al. DNA methylation controls the timing of astrogliogenesis through regulation of JAK-STAT signaling. Development 2005, 132, 3345–3356. [Google Scholar] [CrossRef] [Green Version]
- Smirnova, L.; Grafe, A.; Seiler, A.; Schumacher, S.; Nitsch, R.; Wulczyn, F.G. Regulation of miRNA expression during neural cell specification. Eur. J. Neurosci. 2005, 21, 1469–1477. [Google Scholar] [CrossRef]
- Makeyev, E.V.; Zhang, J.; Carrasco, M.A.; Maniatis, T. The MicroRNA miR-124 promotes neuronal differentiation by triggering brain-specific alternative pre-mRNA splicing. Mol. Cell. 2007, 27, 435–448. [Google Scholar] [CrossRef]
- Krichevsky, A.M.; Sonntag, K.C.; Isacson, O.; Kosik, K.S. Specific microRNAs modulate embryonic stem cell-derived neurogenesis. Stem Cells 2006, 24, 857–864. [Google Scholar] [CrossRef]
- Jiang, S.; Li, C.; McRae, G.; Lykken, E.; Sevilla, J.; Liu, S.Q.; Wan, Y.; Li, Q.J. MeCP2 reinforces STAT3 signaling and the generation of effector CD4+ T cells by promoting miR-124-mediated suppression of SOCS5. Sci. Signal. 2014, 7, ra25. [Google Scholar] [CrossRef]
- Mellios, N.; Feldman, D.A.; Sheridan, S.D.; Ip, J.P.K.; Kwok, S.; Amoah, S.K.; Rosen, B.; Rodriguez, B.A.; Crawford, B.; Swaminathan, R.; et al. MeCP2-regulated miRNAs control early human neurogenesis through differential effects on ERK and AKT signaling. Mol. Psychiatry 2018, 23, 1051–1065. [Google Scholar] [CrossRef]
- Wang, Y.M.; Zheng, Y.F.; Yang, S.Y.; Yang, Z.M.; Zhang, L.N.; He, Y.Q.; Gong, X.H.; Liu, D.; Finnell, R.H.; Qiu, Z.L.; et al. MicroRNA-197 controls ADAM10 expression to mediate MeCP2’s role in the differentiation of neuronal progenitors. Cell Death Differ. 2018. [Google Scholar] [CrossRef]
- Chen, D.; Hu, S.; Wu, Z.; Liu, J.; Li, S. The Role Int. of MiR-132 in Regulating Neural Stem Cell Proliferation, Differentiation and Neuronal Maturation. Cell. Physiol. Biochem. 2018, 47, 2319–2330. [Google Scholar] [CrossRef]
- Namihira, M.; Nakashima, K.; Taga, T. Developmental stage dependent regulation of DNA methylation and chromatin modification in a immature astrocyte specific gene promoter. FEBS Lett. 2004, 572, 184–188. [Google Scholar] [CrossRef] [Green Version]
- Squillaro, T.; Alessio, N.; Capasso, S.; Di Bernardo, G.; Melone, M.A.B.; Peluso, G.; Galderisi, U. Senescence Phenomena and Metabolic Alteration in Mesenchymal Stromal Cells from a Mouse Model of Rett Syndrome. Int. J. Mol. Sci. 2019, 20, 2508. [Google Scholar] [CrossRef]
- Squillaro, T.; Alessio, N.; Cipollaro, M.; Melone, M.A.; Hayek, G.; Renieri, A.; Giordano, A.; Galderisi, U. Reduced expression of MECP2 affects cell commitment and maintenance in neurons by triggering senescence: New perspective for Rett syndrome. Mol. Biol. Cell 2012, 23, 1435–1445. [Google Scholar] [CrossRef]
- Cheval, H.; Guy, J.; Merusi, C.; De, S.D.; Selfridge, J.; Bird, A. Postnatal inactivation reveals enhanced requirement for MeCP2 at distinct age windows. Hum. Mol. Genet. 2012, 21, 3806–3814. [Google Scholar] [CrossRef] [Green Version]
- Robinson, L.; Guy, J.; McKay, L.; Brockett, E.; Spike, R.C.; Selfridge, J.; De, S.D.; Merusi, C.; Riedel, G.; Bird, A.; et al. Morphological and functional reversal of phenotypes in a mouse model of Rett syndrome. Brain 2012, 135, 2699–2710. [Google Scholar] [CrossRef] [Green Version]
- Garg, S.K.; Lioy, D.T.; Cheval, H.; McGann, J.C.; Bissonnette, J.M.; Murtha, M.J.; Foust, K.D.; Kaspar, B.K.; Bird, A.; Mandel, G. Systemic Delivery of MeCP2 Rescues Behavioral and Cellular Deficits in Female Mouse Models of Rett Syndrome. J. Neurosci. 2013, 33, 13612–13620. [Google Scholar] [CrossRef] [Green Version]
- Lang, M.; Wither, R.G.; Colic, S.; Wu, C.; Monnier, P.P.; Bardakjian, B.L.; Zhang, L.; Eubanks, J.H. Rescue of behavioral and EEG deficits in male and female Mecp2-deficient mice by delayed Mecp2 gene reactivation. Hum. Mol. Genet. 2014, 23, 303–318. [Google Scholar] [CrossRef]
- Kron, M.; Lang, M.; Adams, I.T.; Sceniak, M.; Longo, F.; Katz, D.M. A BDNF loop-domain mimetic acutely reverses spontaneous apneas and respiratory abnormalities during behavioral arousal in a mouse model of Rett syndrome. Dis. Models Mech. 2014, 7, 1047–1055. [Google Scholar] [CrossRef] [Green Version]
- Deogracias, R.; Yazdani, M.; Dekkers, M.P.; Guy, J.; Ionescu, M.C.; Vogt, K.E.; Barde, Y.A. Fingolimod, a sphingosine-1 phosphate receptor modulator, increases BDNF levels and improves symptoms of a mouse model of Rett syndrome. Proc. Natl. Acad. Sci. USA 2012, 109, 14230–14235. [Google Scholar] [CrossRef] [Green Version]
- Djukic, A.; Holtzer, R.; Shinnar, S.; Muzumdar, H.; Rose, S.A.; Mowrey, W.; Galanopoulou, A.S.; Shinnar, R.; Jankowski, J.J.; Feldman, J.F.; et al. Pharmacologic Treatment of Rett Syndrome With Glatiramer Acetate. Pediatr. Neurol. 2016, 61, 51–57. [Google Scholar] [CrossRef]
- Kannan, S.; Dai, H.; Navath, R.S.; Balakrishnan, B.; Jyoti, A.; Janisse, J.; Romero, R.; Kannan, R.M. Dendrimer-based postnatal therapy for neuroinflammation and cerebral palsy in a rabbit model. Sci. Transl. Med. 2012, 4, 130ra46. [Google Scholar] [CrossRef]
- Kobayashi, K.; Imagama, S.; Ohgomori, T.; Hirano, K.; Uchimura, K.; Sakamoto, K.; Hirakawa, A.; Takeuchi, H.; Suzumura, A.; Ishiguro, N.; et al. Minocycline selectively inhibits M1 polarization of microglia. Cell Death Dis. 2013, 4, e525. [Google Scholar] [CrossRef]
- Alvarez, J.I.; Katayama, T.; Prat, A. Glial influence on the blood brain barrier. Glia 2013, 61, 1939–1958. [Google Scholar] [CrossRef] [Green Version]
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Kahanovitch, U.; Patterson, K.C.; Hernandez, R.; Olsen, M.L. Glial Dysfunction in MeCP2 Deficiency Models: Implications for Rett Syndrome. Int. J. Mol. Sci. 2019, 20, 3813. https://doi.org/10.3390/ijms20153813
Kahanovitch U, Patterson KC, Hernandez R, Olsen ML. Glial Dysfunction in MeCP2 Deficiency Models: Implications for Rett Syndrome. International Journal of Molecular Sciences. 2019; 20(15):3813. https://doi.org/10.3390/ijms20153813
Chicago/Turabian StyleKahanovitch, Uri, Kelsey C. Patterson, Raymundo Hernandez, and Michelle L. Olsen. 2019. "Glial Dysfunction in MeCP2 Deficiency Models: Implications for Rett Syndrome" International Journal of Molecular Sciences 20, no. 15: 3813. https://doi.org/10.3390/ijms20153813