nach oben

Neurotoxicity Research

Erschienen in:

01.07.2016 | Original Article

Association Between Microglia, Inflammatory Factors, and Complement with Loss of Hippocampal Mossy Fiber Synapses Induced by Trimethyltin

verfasst von: Andrew D. Kraft, Christopher A. McPherson, G. Jean Harry

Erschienen in: Neurotoxicity Research | Ausgabe 1/2016

Einloggen, um Zugang zu erhalten

Abstract

Complement-associated factors are implicated in pathogen presentation, neurodegeneration, and microglia resolution of tissue injury. To characterize complement activation with microglial clearance of degenerating mossy fiber boutons, hippocampal dentate granule neurons were ablated in CD-1 mice with trimethyltin (TMT; 2.2 mg/kg, i.p.). Neuronal apoptosis was accompanied by amoeboid microglia and elevations in tumor necrosis factor [Tnfa], interleukin 1β [Il1b], and Il6 mRNA and C1q protein. Inos mRNA levels were unaltered. Silver degeneration and synaptophysin staining indicated loss of synaptic innervation to CA3 pyramidal neurons. Reactive microglia with thickened bushy morphology showed co-localization of synaptophysin+ fragments. The initial response at 2 days post-TMT included transient elevations in Tnfa, Il1b, Il6, and Inos mRNA levels. A concurrent increase at 2 days was observed in arginase-1 [Arg1], Il10, transforming growth factor β1 [Tgfb1], and chitinase 3 like-3 [Ym1] mRNA levels. At 2 days, C1q protein was evident in the CA3 with elevated C1qa, C1qb, C3, Cr3a, and Cr3b mRNA levels. mRNA levels remained elevated at 5 days, returning to control by 14 days, corresponding to silver degeneration. mRNA levels for pentraxin3 (Ptx3) were elevated on day 2 and Ptx1 was not altered. Our data suggest an association between microglia reactivity, the induction of anti-inflammatory genes concurrent with pro-inflammatory genes and the expression of complement-associated factors with the degeneration of synapses following apoptotic neuronal loss.

Nur mit Berechtigung zugänglich

Afagh A, Cummings BJ, Cribbs DH, Cotman CW, Tenner AJ (1996) Localization and cell association of C1q in Alzheimer’s disease brain. Exp Neurol 138:22–32CrossRefPubMed

Alexander JJ, Anderson AJ, Barnum SR, Stevens B, Tenner AJ (2008) The complement cascade: Yin–Yang in neuroinflammation–neuro-protection and -degeneration. J Neurochem 107:1169–1187CrossRefPubMedPubMedCentral

Barnum SR (1995) Complement biosynthesis in the central nervous system. Crit Rev Oral Biol Med 6:132–146CrossRefPubMed

Benoit ME, Tenner AJ (2011) Complement protein C1q-mediated neuroprotection is correlated with regulation of neuronal gene and microRNA expression. J Neurosci 31:3459–3469CrossRefPubMedPubMedCentral

Benoit ME, Hernandez MX, Dinh ML, Benavente F, Vasquez O, Tenner AJ (2013) C1q-induced LRP1B and GPR6 proteins expressed early in Alzheimer disease mouse models, are essential for the C1q-mediated protection against amyloid-beta neurotoxicity. J Biol Chem 288:654–665CrossRefPubMed

Berg A, Zelano J, Stephan A, Thams S, Barres BA, Pekny M, Pekna M, Cullheim S (2012) Reduced removal of synaptic terminals from axotomized spinal motoneurons in the absence of complement C3. Exp Neurol 237:8–17CrossRefPubMed

Bialas AR, Stevens B (2013) TGF-beta signaling regulates neuronal C1q expression and developmental synaptic refinement. Nat Neurosci 16:1773–1782CrossRefPubMedPubMedCentral

Blinzinger K, Kreutzberg G (1968) Displacement of synaptic terminals from regenerating motoneurons by microglial cells. Z Zellforsch Mikrosk Anat 85:145–157CrossRefPubMed

Bohlson SS, O’Conner SD, Hulsebus HJ, Ho M-M, Fraser DA (2014) Complement, C1q, and C1q-related molecules regulate macrophage polarization. Front Immunol 5:402. doi:10.3389/fimmu.2014.00402 CrossRefPubMedPubMedCentral

Bonifati DM, Kishore U (2007) Role of complement in neurodegeneration and neuroinflammation. Mol Immunol 44:999–1010CrossRefPubMed

Boulanger LM (2009) Immune proteins in brain development and synaptic plasticity. Neuron 64:93–109CrossRefPubMed

Brionne TC, Tesseur I, Masliah E, Wyss-Coray T (2003) Loss of TGF-beta 1 leads to increased neuronal cell death and microgliosis in mouse brain. Neuron 40:1133–1145CrossRefPubMed

Bruccoleri A, Brown H, Harry GJ (1998) Cellular localization and temporal elevation of tumor necrosis factor-alpha, interleukin-1 alpha, and transforming growth factor-beta 1 mRNA in hippocampal injury response induced by trimethyltin. J Neurochem 71:1577–1587CrossRefPubMed

Butovsky O, Jedrychowski MP, Moore CS, Cialic R, Lanser AJ, Gabriely G, Koegisperger T, Dake B, Wu PM, Doykan CE, Fanek Z, Liu L, Chen Z, Rothstein JD, Ransohoff RM, Gygi SP, Antel JP, Weiner HL (2014) Identification of a unique TGF-β-dependent molecular and functional signature in microglia. Nat Neurosci 17:131–143CrossRefPubMed

Carroll MC (2004) The complement system in regulation of adaptive immunity. Nat Immunol 5:981–986CrossRefPubMed

Colton CA (2009) Heterogeneity of microglial activation in the innate immune response in the brain. J Neuroimmune Pharmacol 4(4):399–418CrossRefPubMedPubMedCentral

Dalmau I, Finsen B, Zimmer J, González B, Castellano B (1998) Development of microglia in the postnatal rat hippocampus. Hippocampus 8(5):458–474CrossRefPubMed

Depboylu C, Schäfer MK, Schwaeble WJ, Reinhart TA, Maeda H, Mitsuya H, Damadzic R, Rausch DM, Eiden LE, Weihe E (2005) Increase of C1q biosynthesis in brain microglia and macrophages during lentivirus infection in the rhesus macaque is sensitive to antiretroviral treatment with 6-chloro-2′,3′-dideoxyguanosine. Neurobiol Dis 20:12–26CrossRefPubMed

Erdei A, Isaak A, Torok K, Sandor N, Kremlitzka M, Prechl J, Bajtay Z (2009) Expression and role of CR1 and CR2 on B and T lymphocytes under physiological and autoimmune conditions. Mol Immunol 46:2767–2773CrossRefPubMed

Farber K, Cheung G, Mitchell D, Wallis R, Weihe E, Schwaeble W, Kettenmann H (2009) C1q, the recognition subcomponent of the classical pathway of complement, drives microglial activation. J Neurosci Res 87:644–652CrossRefPubMedPubMedCentral

Fiske BK, Brunjes PC (2000) Microglial activation in the developing rat olfactory bulb. Neuroscience 96(4):807–815CrossRefPubMed

Fraser DA, Tenner AJ (2008) Directing an appropriate immune response: the role of defense collagens and other soluble pattern recognition molecules. Curr Drug Targets 9:113–122CrossRefPubMed

Fraser DA, Pisalyaput K, Tenner AJ (2009) C1q enhances microglial clearance of apoptotic neurons and neuronal blebs, and modulates subsequent inflammatory cytokine production. J Neurochem 112:733–743CrossRefPubMedPubMedCentral

Funk JA, Gohlke J, Kraft AD, McPherson CA, Collins JB, Harry GJ (2011) Voluntary exercise protects hippocampal neurons from trimethyltin injury: possible role of interleukin-6 to modulate tumor necrosis factor receptor-mediated neurotoxicity. Brain Behav Immun 25:1063–1077CrossRefPubMedPubMedCentral

Hanisch UK, Kettenmann H (2007) Microglia: active sensor and versatile effector cells in the normal and pathologic brain. Nat Neurosci 10(11):1387–1394CrossRefPubMed

Harry GJ (2013) Microglia during development and aging. Pharmacol Ther 139:313–326CrossRefPubMedPubMedCentral

Harry GJ, Goodrum JF, Krigman MR, Morell P (1985) The use of Synapsin I as a biochemical marker for neuronal damage by trimethyltin. Brain Res 4(326):9–18CrossRef

Harry GJ, Lefebvre d’Hellencourt C, McPherson CA, Funk JA, Aoyama M, Wine RN (2008) Tumor necrosis factor p55 and p75 receptors are involved in chemical-induced apoptosis of dentate granule neurons. J Neurochem 106:281–298CrossRefPubMed

Harry GJ, Hooth MJ, Behl M, Travlos GS, Howard JL, Price CJ, McBride S, Mervis R, Mouton PR (2014) Developmental neurotoxicity of 3,3′,4,4′-tetrachloroazobenzene with thyroxine deficit: sensitivity of glia and dentate granule neurons in the absence of behavioral changes. Toxics 2(3):496–532CrossRefPubMedPubMedCentral

Henrich-Noack P, Prehn JH, Krieglstein J (1996) TGF-beta 1 protects hippocampal neurons against degeneration caused by transient global ischemia. Dose–response relationship and potential neuroprotective mechanisms. Stroke 27:1609–1614CrossRefPubMed

Henze DA, Urban NN, Barrionuevo G (2000) The multifarious hippocampal mossy fiber pathway: a review. Neuroscience 98:407–427CrossRefPubMed

Huang J, Kim LJ, Mealey R, Marsh HC Jr, Zhang Y, Tenner AJ, Connolly ES Jr, Pinsky DJ (1999) Neuronal protection in stroke by an sLex-glycosylated complement inhibitory protein. Science 285:595–599CrossRefPubMed

Jensen MB, Hegelund IV, Poulsen FR, Owens T, Zimmer J, Finsen B (1999) Microglial reactivity correlates to the density and the myelination of the anterogradely degenerating axons and terminals following perforant path denervation of the mouse fascia dentata. Neuroscience 93:507–518CrossRefPubMed

Johnson SA, Lampert-Etchells M, Pasinetti GM, Rozovsky I, Finch CE (1992) Complement mRNA in the mammalian brain: responses to Alzheimer’s disease and experimental brain lesioning. Neurobiol Aging 13:641–648CrossRefPubMed

Kanaan NM, Kordower JH, Collier TJ (2008) Age and region-specific responses of microglia, but not astrocytes, suggest a role in selective vulnerability of dopamine neurons after 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine exposure in monkeys. Glia 56(11):1199–1214CrossRefPubMedPubMedCentral

Karperien A, Ahammer H, Jelinek HF (2013) Quantitating the subtleties of microglial morphology with fractal analysis. Front Cell Neurosci 7:3. doi:10.3389/fncel.2013.00003 CrossRefPubMedPubMedCentral

Kettenmann H, Kirchhoff F, Verkhratsky A (2013) Microglia: new roles for the synaptic stripper. Neuron 77:10–18CrossRefPubMed

Kouser L, Madhukaran SP, Shastri A, Saraon A, Ferluga J, Al-Mozaini M, Kishore U (2015) Emerging and novel functions of complement protein C1q. Front Immunol 6:317. doi:10.3389/fimmu.2015.00317 CrossRefPubMedPubMedCentral

Lattanzi W, Corvino V, Di Maria V, Michetti F, Geloso MC (2013) Gene expression profiling as a tool to investigate the molecular machinery activated during hippocampal neurodegeneration induced by trimethyltin (TMT) administration. Int J Mol Sci 14:16817–16835CrossRefPubMedPubMedCentral

Liva SM, Kahn MA, Dopp JM, de Vellis J (1999) Signal transduction pathways induced by GM-CSF in microglia: significance in the control of proliferation. Glia 26:344–352CrossRefPubMed

Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2(−Delta Delta C(T)) method. Methods 25:402–408CrossRefPubMed

Lodge PA, Sriram S (1996) Regulation of microglial activation by TGF-beta, IL-10, and CSF-1. J Leukoc Biol 60:502–508PubMed

Lynch NJ, Willis CL, Nolan CC, Roscher S, Fowler MJ, Weihe E, Ray DE, Schwaeble WJ (2004) Microglial activation and increased synthesis of complement component C1q precedes blood–brain barrier dysfunction in rats. Mol Immunol 40:709–716CrossRefPubMed

Manders EMM, Verbeek FJ, Aten JA (1993) Measurement of co-localization of objects in dual-colour confocal images. J Microsc 169:375–382CrossRef

McPherson CA, Merrick BA, Harry GJ (2014) In vivo molecular markers for pro-inflammatory cytokine M1 stage and resident microglia in trimethyltin-induced hippocampal injury. Neurotox Res 25:45–56CrossRefPubMed

Michailidou I, Wilems JG, Kooi EJ, van Eden C, Gold SM, Geurts JJ, Baas R, Huitinga I, Ramaglia V (2015) Complement C1q-C3-associated synaptic changes in multiple sclerosis hippocampus. Ann Neurol 77:1007–1026CrossRefPubMed

Moran LB, Graeber MB (2004) The facial nerve axotomy model. Brain Res Brain Res Rev 44:154–178CrossRefPubMed

Ogden CA, Elkon KB (2006) Role of complement and other innate immune mechanisms in the removal of apoptotic cells. Curr Dir Autoimmun 9:120–142PubMed

Ogita K, Nishiyama N, Sugiyama C, Higuchi K, Yoneyama M, Yoneda Y (2005) Regeneration of granule neurons after lesioning of hippocampal dentate gyrus: evaluation using adult mice treated with trimethyltin chloride as a model. J Neurosci Res 82:609–621CrossRefPubMed

Orlowski D, Slotys Z, Janeczko K (2003) Morphological development of microglia in the postnatal rat brain. A quantitative study. Int J Dev Neurosci 21:445–450CrossRefPubMed

Pasinetti GM, Johnson SA, Rozovsky I, Lampert-Etchells M, Morgan DG, Gordon MN, Morgan TE, Willoughby D, Finch CE (1992) Complement C1qB and C4 mRNAs responses to lesioning in rat brain. Exp Neurol 118:117–125CrossRefPubMed

Perry VH, O’Connor V (2010) The role of microglia in synaptic stripping and synaptic degeneration: a revised perspective. ASN Neuro 2(5):e00047. doi:10.1042/AN20100024 PubMed

Pisalyaput K, Tenner AJ (2008) Complement component C1q inhibits beta-amyloid- and serum amyloid P-induced neurotoxicity via caspase- and calpain-independent mechanisms. J Neurochem 104:696–707PubMed

Planas AM, Soriano MA, Berruezo M, Justicia C, Estrada A, Pitarch S, Ferrer I (1996) Induction of Stat3, a signal transducer and transcription factor, in reactive microglia following transient focal cerebral ischaemia. Eur J Neurosci 8:2612–2618CrossRefPubMed

Ransohoff RM, Perry VH (2009) Microglial physiology: unique stimuli, specialized responses. Ann Rev Immunol 27:119–145CrossRef

Ransohoff RM, Stevens B (2011) Neuroscience. How many cell types does it take to wire a brain? Science 333:1391–1392CrossRefPubMed

Rao K, Lund RD (1993) Optic nerve degeneration induces the expression of MHC antigens in the rat visual system. J Comp Neurol 336:613–627CrossRefPubMed

Rasband WS (1997–2015) ImageJ. U.S. National Institutes of Health, Bethesda. http://imagej.nih.gov/ij/. Accessed 15 Jan 2016

Ricklin D, Hajishengallis G, Yang K, Lambris JD (2010) Complement: a key system for immune surveillance and homeostasis. Nat Immunol 11:785–797CrossRefPubMedPubMedCentral

Rogister B, Delree P, Leprince P, Martin D, Sadzot C, Malgrange B, Munaut C, Rigo JM, Lefebvre PP, Octave JN et al (1993) Transforming growth factor beta as a neuronoglial signal during peripheral nervous system response to injury. J Neurosci Res 34:32–43CrossRefPubMed

Rosen AM, Stevens B (2010) The role of the classical complement cascade in synapse loss during development and glaucoma. Adv Exp Med Biol 703:75–93CrossRefPubMed

Rozovsky I, Morgan TE, Willoughby DA, Dugichi-Djordjevich MM, Pasinetti GM, Johnson SA, Finch CE (1994) Selective expression of clusterin (SGP-2) and complement C1qB and C4 during responses to neurotoxins in vivo and in vitro. Neuroscience 62:741–758CrossRefPubMed

Schafer DP, Stevens B (2013) Phagocytic glial cells: sculpting synaptic circuits in the developing nervous system. Curr Opin Neurobiol 23:1034–1040CrossRefPubMedPubMedCentral

Schafer MK, Schwaeble WJ, Post C, Salvati P, Calabresi M, Sim RB, Petry F, Loos M, Weihe E (2000) Complement C1q is dramatically up-regulated in brain microglia in response to transient global cerebral ischemia. J Immunol 164:5446–5452CrossRefPubMed

Sellar GC, Reid KBM (1990) Molecular cloning and alignment of the genes coding for the A, B, and C chains of human C1q of the serum complement system. Biochem J 274:481–490CrossRef

Shi Q, Colodner KJ, Matousek SB, Merry K, Hong S, Kenison JE, Frost JL, Le KX, Li S, Dodart JC, Caldarone BJ, Stevens B, Lemere CA (2015) Complement C3-deficient mice fail to display age-related hippocampal decline. J Neurosci 35:13029–13042CrossRefPubMed

Sjoberg AP, Trouw LA, Blom AM (2009) Complement activation and inhibition: a delicate balance. Trends Immunol 30:83–90CrossRefPubMed

Stevens B, Allen NJ, Vazquez LE, Howell GR, Christopherson KS, Nouri N, Micheva KD, Mehalow AK, Huberman AD, Stafford B, Sher A, Litke AM, Lambris JD, Smith SJ, John SW, Barres BA (2007) The classical complement cascade mediates CNS synapse elimination. Cell 131:1164–1178CrossRefPubMed

Svensson M, Aldskogius H (1993) Synaptic density of axotomized hypoglossal motorneurons following pharmacological blockade of the microglial cell proliferation. Exp Neurol 120:123–131CrossRefPubMed

Takano M, Kawabata S, Komaki Y, Shibata S, Hikishima K, Toyama Y, Okano H, Nakamura M (2014) Inflammatory cascades mediate synapse elimination in spinal cord compression. J Neuroinflamm 11:40. doi:10.1186/1742-2094-11-40 CrossRef

Takizawa F, Tsuji S, Nagasawa S (1996) Enhancement of macrophage phagocytosis upon iC3b deposition on apoptotic cells. FEBS Lett 397:269–272CrossRefPubMed

Tenner AJ, Frank MM (1987) A sensitive specific hemolytic assay for proenzyme C1. Complement 4:42–52PubMed

Terai K, Walker DG, McGeer EG, McGeer PL (1997) Neurons express proteins of the classical complement pathway in Alzheimer disease. Brain Res 769:385–390CrossRefPubMed

Trapp BD, Wujek JR, Criste GA, Jalabi W, Yin X, Kidd GJ, Stohlman S, Ransohoff R (2007) Evidence for synaptic stripping by cortical microglia. Glia 55:360–368CrossRefPubMed

Tremblay ME, Lowery RL, Majewska AK (2010) Microglial interactions with synapses are modulated by visual experience. PLoS Biol 8:e1000527CrossRefPubMedPubMedCentral

Tremblay ME, Stevens B, Sierra A, Wake H, Bessis A, Nimmerjahn A (2011) The role of microglia in the healthy brain. J Neurosci 31:16064–16069CrossRefPubMed

Trouw LA, Blom AM, Gasque P (2008) Role of complement and complement regulators in the removal of apoptotic cells. Mol Immunol 45:1199–1207CrossRefPubMed

Valverde F (1998) Golgi atlas of the postnatal mouse brain. Springer, New YorkCrossRef

van Kooten C, Fiore N, Trouw LA, Csomor E, Xu W, Castellano G, Daha MR, Gelderman KA (2008) Complement production and regulation by dendritic cells: molecular switches between tolerance and immunity. Mol Immnol 45:4064–4072CrossRef

Veerhuis R, Nielsen HM, Tenner AJ (2011) Complement in the brain. Mol Immunol 48:1592–1603CrossRefPubMedPubMedCentral

Wake H, Moorhouse AJ, Jinno S, Kohsaka S, Nabekura J (2009) Resting microglia directly monitor the functional state of synapses in vivo and determine the fate of ischemic terminals. J Neurosci 29:3974–3980CrossRefPubMed

Webster SD, Park M, Fonseca MI, Tenner AJ (2000) Structural and functional evidence for microglial expression of C1qR(P), the C1q receptor that enhances phagocytosis. J Leukoc Biol 67:109–116PubMed

Weinstein JR, Quan Y, Hanson JF, Colonna L, Iorga M, Honda S, Shibuya K, Shibuya A, Elkon KB, Möller T (2015) IgM-dependent phagocytosis in microglia is mediated by complement receptor 3, not Fcα/μ receptor. J Immunol 195:5309–5317CrossRefPubMed

Wilms H, Hartmann D, Sievers J (1997) Ramification of microglia, monocytes and macrophages in vitro: influences of various epithelial and mesenchymal cells and their conditioned media. Cell Tissue Res 287:447–458CrossRefPubMed

Woodruff TM, Costantini KJ, Crane JW, Atkin JD, Monk PN, Taylor SM, Noakes PG (2008) The complement factor C5a contributes to pathology in a rat model of amyotrophic lateral sclerosis. J Immunol 181:8727–8734CrossRefPubMed

Yu JX, Bradt BM, Cooper NR (2002) Constitutive expression of proinflammatory complement components by subsets of neurons in the central nervous system. J Neuroimmunol 123:91–101CrossRefPubMed

Zhan Y, Paolicelli RC, Sforazzini F, Weinhard L, Bolasco G, Pagani F, Vyssotski AL, Bifone A, Gozzi A, Ragozzino D, Gross CT (2014) Deficient neuron-microglia signaling results in impaired functional brain connectivity and social behavior. Nat Neurosci 17:400–406CrossRefPubMed

Zhou J, Ludlow LE, Hasang W, Rogerson SJ, Jaworowski A (2012) Opsonization of malaria-infected erythrocytes activates the inflammasome and enhances inflammatory cytokine secretion by human macrophages. Malar J 11:343CrossRefPubMedPubMedCentral

Titel: Association Between Microglia, Inflammatory Factors, and Complement with Loss of Hippocampal Mossy Fiber Synapses Induced by Trimethyltin
verfasst von: Andrew D. Kraft
Christopher A. McPherson
G. Jean Harry
Publikationsdatum: 01.07.2016
Verlag: Springer US
Erschienen in: Neurotoxicity Research / Ausgabe 1/2016
Print ISSN: 1029-8428
Elektronische ISSN: 1476-3524
DOI: https://doi.org/10.1007/s12640-016-9606-8

Leitlinien kompakt für die Neurologie

Mit medbee Pocketcards sicher entscheiden.

^{Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag}

Kostenlos registrieren

Neu im Fachgebiet Neurologie

Demenzkranke durch Antipsychotika vielfach gefährdet

Demenz Nachrichten

Der Einsatz von Antipsychotika gegen psychische und Verhaltenssymptome in Zusammenhang mit Demenzerkrankungen erfordert eine sorgfältige Nutzen-Risiken-Abwägung. Neuen Erkenntnissen zufolge sind auf der Risikoseite weitere schwerwiegende Ereignisse zu berücksichtigen.

Nicht Creutzfeldt Jakob, sondern Abführtee-Vergiftung

29.05.2024 Hyponatriämie Nachrichten

Eine ältere Frau trinkt regelmäßig Sennesblättertee gegen ihre Verstopfung. Der scheint plötzlich gut zu wirken. Auf Durchfall und Erbrechen folgt allerdings eine Hyponatriämie. Nach deren Korrektur kommt es plötzlich zu progredienten Kognitions- und Verhaltensstörungen.

Schutz der Synapsen bei Alzheimer

29.05.2024 Morbus Alzheimer Nachrichten

Mit einem Neurotrophin-Rezeptor-Modulator lässt sich möglicherweise eine bestehende Alzheimerdemenz etwas abschwächen: Erste Phase-2-Daten deuten auf einen verbesserten Synapsenschutz.

Sozialer Aufstieg verringert Demenzgefahr

24.05.2024 Demenz Nachrichten

Ein hohes soziales Niveau ist mit die beste Versicherung gegen eine Demenz. Noch geringer ist das Demenzrisiko für Menschen, die sozial aufsteigen: Sie gewinnen fast zwei demenzfreie Lebensjahre. Umgekehrt steigt die Demenzgefahr beim sozialen Abstieg.

Update Neurologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Live-Webinar "Urologie und Sexualmedizin in der Praxis"

Springer Medizin

Abstract

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 1/2016

L-DOPA Reverses the Increased Free Amino Acids Tissue Levels Induced by Dopamine Depletion and Rises GABA and Tyrosine in the Striatum

Overexpressed Down Syndrome Cell Adhesion Molecule (DSCAM) Deregulates P21-Activated Kinase (PAK) Activity in an In Vitro Neuronal Model of Down Syndrome: Consequences on Cell Process Formation and Extension

Role of Nurr1 in the Generation and Differentiation of Dopaminergic Neurons from Stem Cells

Abstract from the 2015 Neurotoxicity Society Meeting: Poster Abstracts

An Acute Methamphetamine Injection Downregulates the Expression of Several Histone Deacetylases (HDACs) in the Mouse Nucleus Accumbens: Potential Regulatory Role of HDAC2 Expression