Age-dependent decrease in glutamine synthetase expression in the hippocampal astroglia of the triple transgenic Alzheimer's disease mouse model: mechanism for deficient glutamatergic transmission?

. 2011 Jul 30 ; 6 () : 55. [epub] 20110730

Status PubMed-not-MEDLINE Jazyk angličtina Země Anglie, Velká Británie Médium electronic

Typ dokumentu časopisecké články

Perzistentní odkaz   https://www.medvik.cz/link/pmid21801442

Astrocytes are fundamental for brain homeostasis and the progression and outcome of many neuropathologies including Alzheimer's disease (AD). In the triple transgenic mouse model of AD (3xTg-AD) generalised hippocampal astroglia atrophy precedes a restricted and specific β-amyloid (Aβ) plaque-related astrogliosis. Astrocytes are critical for CNS glutamatergic transmission being the principal elements of glutamate homeostasis through maintaining its synthesis, uptake and turnover via glutamate-glutamine shuttle. Glutamine synthetase (GS), which is specifically expressed in astrocytes, forms glutamine by an ATP-dependent amination of glutamate. Here, we report changes in GS astrocytic expression in two major cognitive areas of the hippocampus (the dentate gyrus, DG and the CA1) in 3xTg-AD animals aged between 9 and 18 months. We found a significant reduction in Nv (number of cell/mm3) of GS immunoreactive (GS-IR) astrocytes starting from 12 months (28.59%) of age in the DG, and sustained at 18 months (31.65%). CA1 decrease of GS-positive astrocytes Nv (33.26%) occurs at 18 months. This Nv reduction of GS-IR astrocytes is paralleled by a decrease in overall GS expression (determined by its optical density) that becomes significant at 18 months (21.61% and 19.68% in DG and CA1, respectively). GS-IR Nv changes are directly associated with the presence of Aβ deposits showing a decrease of 47.92% as opposed to 23.47% in areas free of Aβ. These changes in GS containing astrocytes and GS-immunoreactivity indicate AD-related impairments of glutamate homeostatic system, at the advanced and late stages of the disease, which may affect the efficacy of glutamatergic transmission in the diseased brain that may contribute to the cognitive deficiency.

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Pellerin L, Bouzier-Sore AK, Aubert A, Serres S, Merle M, Costalat R, Magistretti PJ. Activity-dependent regulation of energy metabolism by astrocytes: an update. Glia. 2007;55:1251–1262. doi: 10.1002/glia.20528. PubMed DOI

Magistretti PJ. Role of glutamate in neuron-glia metabolic coupling. Am J Clin Nutr. 2009;90:875S–880S. doi: 10.3945/ajcn.2009.27462CC. PubMed DOI

Simard M, Nedergaard M. The neurobiology of glia in the context of water and ion homeostasis. Neuroscience. 2004;129:877–896. doi: 10.1016/j.neuroscience.2004.09.053. PubMed DOI

Kofuji P, Newman EA. Potassium buffering in the central nervous system. Neuroscience. 2004;129:1045–1056. PubMed PMC

Verkhratsky A, Parpura V, Rodriguez JJ. Where the thoughts dwell: The physiology of neuronal-glial "diffuse neural net". Brain Res Rev. 2011;66:133–151. doi: 10.1016/j.brainresrev.2010.05.002. PubMed DOI

Halassa MM, Haydon PG. Integrated brain circuits: astrocytic networks modulate neuronal activity and behavior. Annu Rev Physiol. 2010;72:335–355. PubMed PMC

Perea G, Navarrete M, Araque A. Tripartite synapses: astrocytes process and control synaptic information. Trends Neurosci. 2009;32:421–431. doi: 10.1016/j.tins.2009.05.001. PubMed DOI

Wilhelmsson U, Bushong EA, Price DL, Smarr BL, Phung V, Terada M, Ellisman MH, Pekny M. Redefining the concept of reactive astrocytes as cells that remain within their unique domains upon reaction to injury. Proc Natl Acad Sci USA. 2006;103:17513–17518. doi: 10.1073/pnas.0602841103. PubMed DOI PMC

Danbolt NC. Glutamate uptake. Prog Neurobiol. 2001;65:1–105. doi: 10.1016/S0301-0082(00)00067-8. PubMed DOI

Grosche J, Matyash V, Moller T, Verkhratsky A, Reichenbach A, Kettenmann H. Microdomains for neuron-glia interaction: parallel fiber signaling to Bergmann glial cells. Nat Neurosci. 1999;2:139–143. doi: 10.1038/5692. PubMed DOI

Araque A, Parpura V, Sanzgiri RP, Haydon PG. Tripartite synapses: glia, the unacknowledged partner. Trends Neurosci. 1999;22:208–215. doi: 10.1016/S0166-2236(98)01349-6. PubMed DOI

Kvamme E. Synthesis of glutamate and its regulation. Prog Brain Res. 1998;116:73–85. PubMed

McKenna MC. The glutamate-glutamine cycle is not stoichiometric: fates of glutamate in brain. J Neurosci Res. 2007;85:3347–3358. doi: 10.1002/jnr.21444. PubMed DOI

Kirischuk S, Kettenmann H, Verkhratsky A. Membrane currents and cytoplasmic sodium transients generated by glutamate transport in Bergmann glial cells. Pflugers Arch. 2007;454:245–252. doi: 10.1007/s00424-007-0207-5. PubMed DOI

Gras G, Samah B, Hubert A, Leone C, Porcheray F, Rimaniol AC. EAAT expression by macrophages and microglia: still more questions than answers. Amino Acids. 2011. PubMed

Takasaki C, Yamasaki M, Uchigashima M, Konno K, Yanagawa Y, Watanabe M. Cytochemical and cytological properties of perineuronal oligodendrocytes in the mouse cortex. Eur J Neurosci. 2010;32:1326–1336. doi: 10.1111/j.1460-9568.2010.07377.x. PubMed DOI

Deitmer JW, Broer A, Broer S. Glutamine efflux from astrocytes is mediated by multiple pathways. J Neurochem. 2003;87:127–135. doi: 10.1046/j.1471-4159.2003.01981.x. PubMed DOI

Walton HS, Dodd PR. Glutamate-glutamine cycling in Alzheimer's disease. Neurochem Int. 2007;50:1052–1066. doi: 10.1016/j.neuint.2006.10.007. PubMed DOI

Choi DW. Excitotoxic cell death. J Neurobiol. 1992;23:1261–1276. doi: 10.1002/neu.480230915. PubMed DOI

Giaume C, Kirchhoff F, Matute C, Reichenbach A, Verkhratsky A. Glia: the fulcrum of brain diseases. Cell Death Differ. 2007;14:1324–1335. doi: 10.1038/sj.cdd.4402144. PubMed DOI

Nedergaard M, Rodriguez JJ, Verkhratsky A. Glial calcium and diseases of the nervous system. Cell Calcium. 2010;47:140–149. doi: 10.1016/j.ceca.2009.11.010. PubMed DOI

Heneka MT, Rodriguez JJ, Verkhratsky A. Neuroglia in neurodegeneration. Brain Res Rev. 2010;63:189–211. doi: 10.1016/j.brainresrev.2009.11.004. PubMed DOI

Verkhratsky A, Olabarria M, Noristani HN, Yeh CY, Rodriguez JJ. Astrocytes in Alzheimer's disease. Neurotherapeutics. 2010;7:399–412. doi: 10.1016/j.nurt.2010.05.017. PubMed DOI PMC

Samland H, Huitron-Resendiz S, Masliah E, Criado J, Henriksen SJ, Campbell IL. Profound increase in sensitivity to glutamatergic- but not cholinergic agonist-induced seizures in transgenic mice with astrocyte production of IL-6. J Neurosci Res. 2003;73:176–187. doi: 10.1002/jnr.10635. PubMed DOI

Aloisi F, Care A, Borsellino G, Gallo P, Rosa S, Bassani A, Cabibbo A, Testa U, Levi G, Peschle C. Production of hemolymphopoietic cytokines (IL-6, IL-8, colony-stimulating factors) by normal human astrocytes in response to IL-1 beta and tumor necrosis factor-alpha. J Immunol. 1992;149:2358–2366. PubMed

Nedergaard M, Dirnagl U. Role of glial cells in cerebral ischemia. Glia. 2005;50:281–286. doi: 10.1002/glia.20205. PubMed DOI

Walsh DM, Selkoe DJ. A beta oligomers - a decade of discovery. J Neurochem. 2007;101:1172–1184. doi: 10.1111/j.1471-4159.2006.04426.x. PubMed DOI

Braak E, Griffing K, Arai K, Bohl J, Bratzke H, Braak H. Neuropathology of Alzheimer's disease: what is new since A. Alzheimer? Eur Arch Psychiatry Clin Neurosci. 1999;249(Suppl 3):14–22. PubMed

Yankner BA. Mechanisms of neuronal degeneration in Alzheimer's disease. Neuron. 1996;16:921–932. doi: 10.1016/S0896-6273(00)80115-4. PubMed DOI

Pekny M, Nilsson M. Astrocyte activation and reactive gliosis. Glia. 2005;50:427–434. doi: 10.1002/glia.20207. PubMed DOI

Noristani HN, Olabarria M, Verkhratsky A, Rodriguez JJ. Serotonin fibre sprouting and increase in serotonin transporter immunoreactivity in the CA1 area of hippocampus in a triple transgenic mouse model of Alzheimer's disease. Eur J Neurosci. 2010;32:71–79. doi: 10.1111/j.1460-9568.2010.07274.x. PubMed DOI

Olabarria M, Noristani HN, Verkhratsky A, Rodriguez JJ. Concomitant astroglial atrophy and astrogliosis in a triple transgenic animal model of Alzheimer's disease. Glia. 2010;58:831–838. PubMed

Rodriguez JJ, Olabarria M, Chvatal A, Verkhratsky A. Astroglia in dementia and Alzheimer's disease. Cell Death Differ. 2009;16:378–385. doi: 10.1038/cdd.2008.172. PubMed DOI

Oddo S, Caccamo A, Kitazawa M, Tseng BP, LaFerla FM. Amyloid deposition precedes tangle formation in a triple transgenic model of Alzheimer's disease. Neurobiol Aging. 2003;24:1063–1070. doi: 10.1016/j.neurobiolaging.2003.08.012. PubMed DOI

Oddo S, Caccamo A, Shepherd JD, Murphy MP, Golde TE, Kayed R, Metherate R, Mattson MP, Akbari Y, LaFerla FM. Triple-transgenic model of Alzheimer's disease with plaques and tangles: intracellular Abeta and synaptic dysfunction. Neuron. 2003;39:409–421. doi: 10.1016/S0896-6273(03)00434-3. PubMed DOI

Rodriguez JJ, Jones VC, Tabuchi M, Allan SM, Knight EM, LaFerla FM, Oddo S, Verkhratsky A. Impaired adult neurogenesis in the dentate gyrus of a triple transgenic mouse model of Alzheimer's disease. PLoS One. 2008;3:e2935. doi: 10.1371/journal.pone.0002935. PubMed DOI PMC

Rodriguez JJ, Jones VC, Verkhratsky A. Impaired cell proliferation in the subventricular zone in an Alzheimer's disease model. Neuroreport. 2009;20:907–912. doi: 10.1097/WNR.0b013e32832be77d. PubMed DOI

Paxinos G, Franklin KBJ. The mouse brain in stereotaxic coordinates. Elsevier: Academic Press; 2004.

Wilhelmsson U, Li L, Pekna M, Berthold CH, Blom S, Eliasson C, Renner O, Bushong E, Ellisman M, Morgan TE, Pekny M. Absence of glial fibrillary acidic protein and vimentin prevents hypertrophy of astrocytic processes and improves post-traumatic regeneration. J Neurosci. 2004;24:5016–5021. doi: 10.1523/JNEUROSCI.0820-04.2004. PubMed DOI PMC

Eng LF, Ghirnikar RS, Lee YL. Glial fibrillary acidic protein: GFAP-thirty-one years (1969-2000) Neurochem Res. 2000;25:1439–1451. doi: 10.1023/A:1007677003387. PubMed DOI

Aksenov MY, Aksenova MV, Butterfield DA, Hensley K, Vigo-Pelfrey C, Carney JM. Glutamine synthetase-induced enhancement of beta-amyloid peptide A beta (1-40) neurotoxicity accompanied by abrogation of fibril formation and A beta fragmentation. J Neurochem. 1996;66:2050–2056. PubMed

Hensley K, Hall N, Subramaniam R, Cole P, Harris M, Aksenov M, Aksenova M, Gabbita SP, Wu JF, Carney JM. et al.Brain regional correspondence between Alzheimer's disease histopathology and biomarkers of protein oxidation. J Neurochem. 1995;65:2146–2156. PubMed

Cordero MI, Rodriguez JJ, Davies HA, Peddie CJ, Sandi C, Stewart MG. Chronic restraint stress down-regulates amygdaloid expression of polysialylated neural cell adhesion molecule. Neuroscience. 2005;133:903–910. doi: 10.1016/j.neuroscience.2005.03.046. PubMed DOI

Alzheimer A. Histologische und Histopathologische Arbeiten über die Grosshirnrinde mit besonderer Berücksichtigung der pathologischen Anatomie der Geisteskrankheiten Jena. Verlag von Gustav Fischer; 1910. Beiträge zur Kenntnis der pathologischen Neuroglia und ihrer Beziehungen zu den Abbauvorgängen im Nervengewebe; pp. 401–562.

Sullivan SM, Lee A, Bjorkman ST, Miller SM, Sullivan RK, Poronnik P, Colditz PB, Pow DV. Cytoskeletal anchoring of GLAST determines susceptibility to brain damage: an identified role for GFAP. J Biol Chem. 2007;282:29414–29423. doi: 10.1074/jbc.M704152200. PubMed DOI

Hughes EG, Maguire JL, McMinn MT, Scholz RE, Sutherland ML. Loss of glial fibrillary acidic protein results in decreased glutamate transport and inhibition of PKA-induced EAAT2 cell surface trafficking. Brain Res Mol Brain Res. 2004;124:114–123. PubMed

Pekny M, Eliasson C, Siushansian R, Ding M, Dixon SJ, Pekna M, Wilson JX, Hamberger A. The impact of genetic removal of GFAP and/or vimentin on glutamine levels and transport of glucose and ascorbate in astrocytes. Neurochem Res. 1999;24:1357–1362. doi: 10.1023/A:1022572304626. PubMed DOI

Weir MD, Thomas DG. Effect of dexamethasone on glutamine synthetase and glial fibrillary acidic protein in normal and transformed astrocytes. Clin Neuropharmacol. 1984;7:303–306. doi: 10.1097/00002826-198412000-00005. PubMed DOI

Fuhrmann M, Bittner T, Jung CK, Burgold S, Page RM, Mitteregger G, Haass C, LaFerla FM, Kretzschmar H, Herms J. Microglial Cx3cr1 knockout prevents neuron loss in a mouse model of Alzheimer's disease. Nat Neurosci. 2010;13:411–413. doi: 10.1038/nn.2511. PubMed DOI PMC

Le Prince G, Delaere P, Fages C, Lefrancois T, Touret M, Salanon M, Tardy M. Glutamine synthetase (GS) expression is reduced in senile dementia of the Alzheimer type. Neurochem Res. 1995;20:859–862. doi: 10.1007/BF00969698. PubMed DOI

Robinson SR. Neuronal expression of glutamine synthetase in Alzheimer's disease indicates a profound impairment of metabolic interactions with astrocytes. Neurochem Int. 2000;36:471–482. doi: 10.1016/S0197-0186(99)00150-3. PubMed DOI

Robinson SR. Changes in the cellular distribution of glutamine synthetase in Alzheimer's disease. J Neurosci Res. 2001;66:972–980. doi: 10.1002/jnr.10057. PubMed DOI

Lievens JC, Woodman B, Mahal A, Spasic-Boscovic O, Samuel D, Kerkerian-Le Goff L, Bates GP. Impaired glutamate uptake in the R6 Huntington's disease transgenic mice. Neurobiol Dis. 2001;8:807–821. doi: 10.1006/nbdi.2001.0430. PubMed DOI

Jacob CP, Koutsilieri E, Bartl J, Neuen-Jacob E, Arzberger T, Zander N, Ravid R, Roggendorf W, Riederer P, Grunblatt E. Alterations in expression of glutamatergic transporters and receptors in sporadic Alzheimer's disease. J Alzheimers Dis. 2007;11:97–116. PubMed

Castegna A, Aksenov M, Aksenova M, Thongboonkerd V, Klein JB, Pierce WM, Booze R, Markesbery WR, Butterfield DA. Proteomic identification of oxidatively modified proteins in Alzheimer's disease brain. Part I: creatine kinase BB, glutamine synthase, and ubiquitin carboxy-terminal hydrolase L-1. Free Radic Biol Med. 2002;33:562–571. doi: 10.1016/S0891-5849(02)00914-0. PubMed DOI

Burbaeva G, Boksha IS, Tereshkina EB, Savushkina OK, Starodubtseva LI, Turishcheva MS. Glutamate metabolizing enzymes in prefrontal cortex of Alzheimer's disease patients. Neurochem Res. 2005;30:1443–1451. doi: 10.1007/s11064-005-8654-x. PubMed DOI

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