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Prof. Dr. Christian Alzheimer

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



Current Lab Members
Fang Zheng, PhD
Tobias Huth, MD PhD
Hans van Brederode, PhD
Andrea Link, PhD student
Sabine Heßler, PhD student
Sandra Lehnert, PhD student
Stephanie Hartmann, PhD student
Theresa Schuy, MD student
Philipp Keßler, MD student


Publications (as listed in Pubmed)

Research Interests

I. Role of Activin in Hippocampal Excitability and Plasticity, Anxiety-like Behavior, and Neuroprotection

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 Medicine 6: 812-815, 2000.
  • Alzheimer C (ed.): Molecular and Cellular Biology of Neuroprotection in the CNS. Kluwer Acad Publ, 2002.
  • 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-b/activin signaling pathways at central synapses. Trends Neurosci 34: 421-429, 2011.

II. Properties and Function of Na and K Channels in CNS Neurons

Using acutely isolated neurons and brain slices, we are investigating properties and functions of sodium currents and inward rectifier potassium currents. In particular, we are studying

  • how these currents are modulated by various neurotransmitters and -modulators,
  • how these currents are regulated by the β-secretase BACE1,
  • how these currents might be involved in CNS disease, and
  • how these currents influence signal processing.

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.
  • Alzheimer C: A novel voltage-dependent cation current in rat neocortical neurones. J Physiol (Lond.) 479: 199-205, 1994.
  • 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.
  • van Brederode J, Takigawa T and Alzheimer C: GABA-evoked chloride currents do not differ between dendrites and somata of rat neocortical neurons. J Physiol (Lond.) 533: 711-716, 2001.
  • Takigawa T and Alzheimer C: Phasic and tonic attenuation of EPSPs by inward rectifier K+ channels in rat hippocampal pyramidal cells. J Physiol (Lond.) 539: 67-75, 2002.
  • Klose A, Huth T, Alzheimer C. U73122 Selectively Inhibits Kir3 and BK Channels in a Phospholipase C-Independent Fashion. Mol Pharmacol 74: 1203-1214, 2008.
  • 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.
  • Huth T, Rittger A, Saftig P, Alzheimer C. b-site APP-cleaving enzyme 1 (BACE1) cleaves cerebellar Na+ channel b4-subunit and promotes Purkinje cell firing by slowing the decay of resurgent Na+ current. Pflügers Archiv - European Journal of Physiology 461: 355-371, 2011.
  • Zheng F, Lammert K, Nixdorf-Bergweiler BE, Steigerwald F, Volkmann J, Alzheimer C. Axonal failure during high frequency stimulation of rat subthalamic nucleus. J Physiol (Lond) 589:2781-2793, 2011.
  • Huth T and Alzheimer C. Voltage-dependent Na+ channels as targets of BACE1 - implications for neuronal firing and beyond. Curr Alzheimer Res 9, 184-188, 2012.
  • 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.
  • 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.

III. Synaptic Integration and Plasticity in Normal Hippocampus and Neuropsychiatric Disease Models

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 mainly use muscarinic receptor knock-out mice to elucidate the muscarinic effects on signal processing and synaptic plasticity.

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

Selected publications:

  • Mittmann T and Alzheimer C: Muscarinic inhibition of persistent Na+ current in rat neocortical pyramidal neurons. J Neurophysiol 79: 1579-1582, 1998.
  • Seeger T and Alzheimer C: Muscarinic activation of inwardly rectifying K+ conductance reduces EPSPs in rat hippocampal CA1 pyramidal cells. J Physiol (Lond.) 535: 383-396, 2001.
  • 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.
  • C. Alzheimer and Wess J: Muskarinische Acetylcholin-Rezeptoren und die neuronalen Mechanismen kognitiver Leistungen. Neuroforum 2.05: 61-66, Elsevier/Spektrum Akademischer Verlag, 2005. 
  • 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.
  • Zheng F, Wess J, Alzheimer C. M2 muscarinic acetylcholine receptors regulate long-term potentiation at hippocampal CA3 pyramidal cell synapses in an input-specific fashion. J Neurophysiol (in press)

Former Research Project: Biological Significance of Ion Channels in Non-Excitable Cells

How does the activity of ion channels influence proliferation and differentiation of non-excitable cells? Do extracellular signaling molecules target ion channels to exert biologically significant actions on non-excitable cells? Does the pharmacological blockade or activation of ion channels have an impact on growth and differentiation? Are altered channel expression pattern associated with diseases? We use human keratinocytes to investigate this kind of questions, employing a combination of electrophysiological and molecular biological techniques (the latter with the help of Prof. Werner, ETH Zurich).

Selected publications:

  • Koegel H and Alzheimer C: Expression and biological significance of Ca2+-activated ion channels in human keratinocytes. FASEB J 15:145-154, 2001.
  • Burgstahler R, Koegel H, Rucker F, Tracey D, Grafe P and Alzheimer C. Confocal ratiometric voltage imaging of cultured human keratinocytes reveals layer-specific responses to ATP. Am J Physiol Cell Physiol 284: C944-C952, 2003.
  • Koegel H, Kaesler S, Burgstahler R, Werner S and Alzheimer C: Unexpected down-regulation of the hIK1 Ca2+-activated K+ channel by its opener 1-EBIO in HaCaT keratinocytes: inverse effects on cell growth and proliferation. J Biol Chem 278: 3323-3330, 2003.