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Prof. Dr. Christian Alzheimer

Institut für Physiologie und Pathophysiologie
Universität Erlangen-Nürnberg
Universitätsstr. 17
91054 Erlangen




Publications (as listed in Pubmed)



Main Research Interests

I. Role of Activin in Hippocampal Excitability and Plasticity, Anxiety-like Behavior, Depression, and Neuroprotection (group leader: Fang Zheng)

Activins belong to the transforming growth factor β (TGF β) superfamily and are now recognized as multifunctional regulatory proteins. Whereas we and others have firmly established a neuroprotective role of activin in acute brain injury, it remained unclear whether activin also influences the operation of neuronal circuits under physiological conditions. To explore the functions of activin in normal adult brain, S. Werner and her group at the Institute of Cell Biology (ETH Zurich) generated transgenic mice expressing a dominant-negative mutant of activin receptor IB (dnActRIB) under the control of the CaMKII-α promoter. In hippocampal slices of dnActRIB mice, we found that the NMDA component of glutamatergic neurotransmission was decreased and, as a consequence, synaptic plasticity was impaired, causing a significant reduction in long-term potentiation (LTP) at the Schaffer-CA1 synapse. These data were the first to demonstrate that endogenously produced activin is capable of modulating the performance of the major excitatory synapse in the brain. We have now extended our study to the role of activin at the GABAergic synapse. GABA is the major inhibitory transmitter in the brain and has been implicated in a broad spectrum of physiological functions and disease states, including anxiety and depression. In behavioral tests, disruption of activin receptor signaling produced a low-anxiety phenotype that failed to respond to benzodiazepines. In whole-cell recordings from hippocampal pyramidal cells, enhanced spontaneous GABA release, increased GABA tonus, reduced benzodiazepine sensitivity and augmented GABAB receptor function emerged as likely substrates of the low-anxiety phenotype. These data provide strong evidence that activin influences pre- and postsynaptic components of GABAergic synapses in a highly synergistic fashion. Given the crucial role of GABAergic neurotransmission in emotional states, anxiety and depression, dysfunctions of activin receptor signaling could be involved in affective disorders and drugs affecting this pathway might show promise for psychopharmacological treatment.

Selected publications:

  • Tretter YP, Hertel M, Munz B, ten Bruggencate G, Werner S and Alzheimer C: Induction of activin A is essential for the neuroprotective action of bFGF in vivo. Nature Med 6: 812-815, 2000.
  • Werner S and Alzheimer C: Roles of activin in tissue repair, fibrosis, and inflammatory disease. Cytokine Growth Factor Rev 17: 157-171, 2006.
  • Müller M, Zheng F, Werner S and Alzheimer C. Transgenic mice expressing dominant-negative activin receptor IB in forebrain neurons reveal novel functions of activin at glutamatergic synapses. J Biol Chem 281:29076-29084, 2006.
  • Zheng F, Adelsberger H, Müller MR, Fritschy J-M, Werner S and Alzheimer C: Activin tunes GABAergic neurotransmission and modulates anxiety-like behavior. Mol Psychiatry 14:332-346, 2009.
  • Krieglstein K, Zheng F, Unsicker K and Alzheimer C. More than being protective: functional roles for TGF-beta/activin signaling pathways at central synapses. Trends Neurosci 34: 421-429, 2011.
  • Link AS, Kurinna S, Havlicek S, Lehnert S, Reichel M, Kornhuber J, Winner B, Huth T, Zheng F, Werner S, Alzheimer C. Kdm6b and Pmepa1 as targets of bioelectrically and behaviorally induced activin A signaling. Mol Neurobiol 53:4210-4225, 2016.
  • Zheng F, Puppel A, Huber SE, Link AS, Eulenburg V, van Brederode JF, Müller CP and Alzheimer C. Activin controls ethanol potentiation of inhibitory synaptic transmission through GABAA receptors and concomitant behavioral sedation. Neuropsychopharmacol 41: 2023-2044, 2016.
  • Link AS, Zheng F and Alzheimer C. Activin signaling in the pathogenesis and therapy of neuropsychiatric diseases. Front Mol Neurosci 2016, doi: 10.3389/fnmol.2016.00032.



II. Properties and Functions of Na+ and K+ Channels and their regulation by BACE1 (group leader: Tobias Huth)

Using brain slices, acutely isolated neurons and heterologous expression systems, we are investigating properties and functions of voltage-dependent Na+ and K+ currents. In particular, we are studying how these currents are modulated by the β-site APP cleaving enzyme 1 (BACE1).

Selected publications:

  • Alzheimer C, Schwindt PC and Crill WE: Modal gating of Na+ channels as a mechanism of persistent Na+ current in pyramidal neurons from rat and cat neocortex. J Neurosci 13: 660-673, 1993
  • Lipowsky R, Gillessen T and Alzheimer C: Dendritic Na+ channels amplify EPSPs in hippocampal CA1 pyramidal cells. J Neurophysiol 76: 2181-2191, 1996.
  • Takigawa T and Alzheimer C: G protein-activated inwardly rectifying K+ (GIRK) currents in dendrites of rat neocortical pyramidal cells. J Physiol (Lond.) 517:385-390, 1999.
  • Huth T, Schmidt-Neuenfeldt K, Rittger A, Saftig P, Reiss K, Alzheimer C. Non-proteolytic effect of ß-site APP- cleaving enzyme 1 (BACE1) on sodium channel function. Neurobiol Dis 33: 282-289, 2009.
  • Sittl R, Lampert A, Huth T, Schuy ET, Link AS, Fleckenstein J, Alzheimer C, Grafe P, Carr RW. Anti-cancer drug oxaliplatin induces acute cooling-aggravated neuropathy via Nav1.6-mediated resurgent and persistent current. Proc Natl Acad Sci (USA) 109:6704-6709, 2012.
  • Hessler S, Zheng F, Hartmann S, Rittger A, Lehnert S, Völkel M, Nissen M, Edelmann E, Saftig P, Schwake M, Huth T, Alzheimer C. β-secretase BACE1 regulates hippocampal and reconstituted M-currents in a β-subunit-like fashion. J Neurosci 35: 3298-3311, 2015.
  • Lehnert S, Hartmann S, Hessler S, Adelsberger H, Huth T and Alzheimer C. Ion channel regulation by β-secretase BACE1- enzymatic and non-enzymatic effects beyond Alzheimer´s disease. Channels 10:365-378, 2016.
  • Hartmann S, Zheng F, Kyncl M, Karch S, Voelkl K, Zott B, D'Avanzo C, Lomoio S, Tesco G, Kim DY*, Alzheimer C, Huth T. β-Secretase BACE1 promotes surface expression and function of Kv3.4 at hippocampal mossy fiber synapses. J Neurosci 38: 3480-3494, 2018


III. Neuropsychiatric disease models and mechanisms of drug action

Although muscarinic receptors are known to play central roles in facilitating cognitive functions, it is still not well understood how activation of individual receptor subtypes (M1 - M5) influences the neurobiological mechanisms that are thought to underlie learning and memory at the cellular and network level. Given the lack of muscarinic receptor ligands with a high degree of receptor subtype selectivity, we have used muscarinic receptor knock-out mice (in collaboration with Jürgen Wess, NIDDK, NIH, USA) to elucidate  muscarinic effects on signal processing and synaptic plasticity. In collaboration with Carmen Villmann (Institute of Clinical Neurobiology, University of Würzburg), we have studied glycinergic neurotransmission in brainstem slices of a mouse model of startle disease. In collaboration with Christian Müller and Johannes Kornhuber (Dept. of Psychiatry, University Hospital Erlangen), we are exploring mechanisms of antipsychotic drug action.

from: Alzheimer & Wess, Neuroforum 2/05, 2005

Selected publications:

  • Seeger T, Fedorova I, Zheng F, Miyakawa T, Koustova E, Gomeza J, Basile AS, Alzheimer C and Wess J. M2 muscarinic acetylcholine receptor knockout mice show deficits in behavioral flexibility, working memory, and hippocampal plasticity. J Neurosci 24:10117-10127, 2004.
  • Sydow A, van der Jeugd A, Zheng F, Ahmed T, Balschun D, Petrova O, Drexler D, Zhou L, Rune G,  Mandelkow E, D'Hooge R, Alzheimer C, Mandelkow EM. Tau-induced defects in synaptic plasticity, learning and memory are reversible in transgenic mice after switching off the toxic tau mutant. J Neurosci 31:2511-2525, 2011.
  • Tischbirek CH, Wenzel EM, Zheng F, Huth T, Amato D, Trapp S, Denker A, Welzel O, Lueke K, Svetlitchny A, Rauh M, Deusser J, Schwab A, Rizzoli SO, Henkel AW, Müller CP, Alzheimer C, Kornhuber J, Groemer TW. Use-dependent inhibition of synaptic transmission by the secretion of intravesicularly accumulated antipsychotic drugs. Neuron 74:830-844, 2012.
  • Schaefer N, Berger A, van Brederode J, Zheng F, Zhang Y, Leacock S, Littau L, Jablonka S, Malhotra S, Topf M, Winter F, Davydova D, Lynch J, Paige C, Alzheimer C, Harvey R, Villmann C. Disruption of a structurally important extracellular element in the glycine receptor leads to decreased synaptic integration and signaling resulting in severe startle disease. J Neurosci 37: 7948-7961, 2017.
  • Schaefer N, Zheng F, van Brederode J, Berger A, Leacock S, Hirata H, Paige CJ, Harvey RJ, Alzheimer C and Villmann C. Functional Consequences of the Postnatal Switch From Neonatal to Mutant Adult Glycine Receptor α1 Subunits in the Shaky Mouse Model of Startle Disease. Frontiers Mol Neurosci doi: 10.3389/fnmol.2018.00167, 2018.
  • Amato D, Canneva F, Cumming P, Maschauer S, Groos D, Wrosch J, Groemer T, Chiofalo L, Dahlmanns M, Zheng F, Kornhuber J, Prante O, Alzheimer C, von Hörsten S, Müller CP. A dopaminergic mechanism of antipsychotic drug efficacy, failure, and failure reversal: the role of the dopamine transporter. Mol Psychiatry, in press
  • Groos D, Zheng F, Rauh M, Quinger B, Kornhuber J, Müller CP, Alzheimer C. Chronic antipsychotic treatment targets GIRK current suppression, loss of LTD, and behavioral sensitization in a mouse model of amphetamine psychosis. J Psychopharmacol, in press