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Institute of Physiology and Pathophysiology

Kann Lab

About us

 

The research in the Kann laboratory has two scientific focuses:

 

1. The human brain has a relatively high energy demand and is very sensitive to shortage of oxygen and glucose. We investigate the neuronal energy metabolism and the functions of mitochondria, in particular during synchronized neuronal network activities that underlie higher brain functions, such as perception and memory, under physiological and pathophysiological conditions.

 

 

 

(a) Combined recordings of the local field potential and the oxygen concentration in the CA3 region of acute hippocampal slices. (b, c) Sample traces of gamma oscillations (30-70 Hz) and sharp wave-ripples (Schneider et al., JCBFM, 2019).

 

 

 

2. The human brain possesses innate immune cells, so-called microglial cells (resident macrophages). Microglia become activated, for example, during injury and infection. We investigate the impact of microglia at different activation stages on neuronal network activities and neurodegeneration.

 

 

(a) Staining with the microglial marker Iba1 in slice cultures exposed to the leukocyte cytokine interferon-γ for 72 h. (b) Stereology-based cell counting of Iba1-positive cells. (c) Sample spectrograms of gamma oscillations from recordings in individual slices. The slowing of gamma oscillations (IFN-γ) is mainly caused by the moderate release of nitric oxide from activated microglia (Ta et al., PNAS, 2019).

 

 

Our basic research provides insights into pathophysiological mechanisms that might have a role in brain diseases, such as multiple sclerosis and Alzheimer's disease.

 

 

Selected publications:

 

Cunnane SC, Trushina E, Morland C, Prigione A, Casadesus G, Andrews ZB, Beal MF, Bergersen LH, Brinton RD, de la Monte S, Eckert A, Harvey J, Jeggo R, Jhamandas JH, Kann O, la Cour MC, Martin WF, Mithieux G, Moreira PI, Murphy MP, Nave K-A, Nuriel T, Oliet SHR, Saudou F, Mattson MP, Swerdlow RH, Millan MJ. Brain energy rescue: an emerging therapeutic concept for neurodegenerative disorders of ageing. Nat Rev Drug Discov. 2020 Sep;19(9):609-633. doi: 10.1038/s41573-020-0072-x.

 

Hollnagel JO, Cesetti T, Schneider J, Vazetdinova A, Valiullina-Rakhmatullina F, Lewen A, Rozov A, Kann O. Lactate attenuates synaptic transmission and affects brain rhythms featuring high energy expenditure. iScience. 2020 Jul 24; 23(7):101316. doi 10.1016/j.isci.2020.101316.

 

Ta TT, Dikmen HO, Schilling S, Chausse B, Lewen A, Hollnagel JO, Kann O. Priming of microglia with IFN-γ slows neuronal gamma oscillations in situ. Proc Natl Acad Sci U S A. 2019 Feb 19;116(10):4637-4642. doi: 10.1073/pnas.1813562116.

 

Schneider J, Berndt N, Papageorgiou IE, Maurer J, Bulik S, Both M, Draguhn A, Holzhütter HG, Kann O. Local oxygen homeostasis during various neuronal network activity states in the mouse hippocampus. J Cereb Blood Flow Metab. 2017 Jan 1:271678X17740091. doi: 10.1177/0271678X17740091. [Epub ahead of print]

 

Papageorgiou IE, Lewen A, Galow LV, Cesetti T, Scheffel J, Regen T, Hanisch UK, Kann O. TLR4-activated microglia require IFN-γ to induce severe neuronal dysfunction and death in situ. Proc Natl Acad Sci U S A. 2016 Jan 5;113(1):212-7.

 

Kann O, Huchzermeyer C, Kovács R, Wirtz S, Schuelke M. Gamma oscillations in the hippocampus require high complex I gene expression and strong functional performance of mitochondria. Brain. 2011 Feb;134(Pt 2):345-58.

 

Kann O, Kovács R, Njunting M, Behrens CJ, Otáhal J, Lehmann TN, Gabriel S, Heinemann U. Metabolic dysfunction during neuronal activation in the ex vivo hippocampus from chronic epileptic rats and humans. Brain. 2005 Oct;128(Pt 10):2396-407. 


Recent Publications

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Alterations of distributed neuronal network oscillations during acute pain in freely-moving mice. IBRO Rep. 2020 Dec;9:195-206. doi: 10.1016/j.ibror.2020.08.001. eCollection 2020 Dec. Epub 2020 Aug 11.

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VEGF-D Downregulation in CA1 Pyramidal Neurons Exerts Asymmetric Changes of Dendritic Morphology without Correlated Electrophysiological Alterations. Neuroscience. 2020 Nov 10;448:28-42. doi: 10.1016/j.neuroscience.2020.09.012. Epub 2020 Sep 11.

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The mitochondrial calcium uniporter is crucial for the generation of fast cortical network rhythms. J Cereb Blood Flow Metab. 2020 Nov;40(11):2225-2239. doi: 10.1177/0271678X19887777. Epub 2019 Nov 13.

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Multifunctional reactive MALDI matrix enabling high-lateral resolution dual polarity MS imaging and lipid C=C position-resolved MS2 imaging. 2020 Oct 20;92(20):14130-14138. doi: 10.1021/acs.analchem.0c03150. Epub 2020 Sep 28.

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Neuronal gamma oscillations and activity-dependent potassium transients remain regular after depletion of microglia in postnatal cortex tissue. J Neurosci Res. 2020 Oct;98(10):1953-1967. doi: 10.1002/jnr.24689. Epub 2020 Jul 7.

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Synchronicity of excitatory inputs drives hippocampal networks to distinct oscillatory patterns. Hippocampus. 2020 Oct;30(10):1044-1057. doi: 10.1002/hipo.23214. Epub 2020 May 15.

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Processing of hippocampal network activity in the receiver network of the medial entorhinal cortex layer V. J Neurosci. 2020 Sep 25:JN-RM-0586-20. doi: 10.1523/JNEUROSCI.0586-20.2020. Online ahead of print.

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Anesthetics and plants: no pain, no brain, and therefore no consciousness. Protoplasma. 2020 Sep 2. doi: 10.1007/s00709-020-01550-9. Online ahead of print.

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Brain energy rescue: an emerging therapeutic concept for neurodegenerative disorders of ageing. Nat Rev Drug Discov. 2020 Sep;19(9):609-633. doi: 10.1038/s41573-020-0072-x. Epub 2020 Jul 24.

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Microglia and lipids: how metabolism controls brain innate immunity. Semin Cell Dev Biol. 2020 Aug 14;S1084-9521(19)30197-1. doi: 10.1016/j.semcdb.2020.08.001. Online ahead of print.

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GM-CSF induces noninflammatory proliferation of microglia and disturbs electrical neuronal network rhythms in situ. J Neuroinflammation. 2020 Aug 11;17(1):235. doi: 10.1186/s12974-020-01903-4.

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Inhibition of cardiac Kv4.3 (Ito) channel isoforms by class I antiarrhythmic drugs lidocaine and mexiletine. Eur J Pharmacol. 2020 Aug 5;880:173159. doi: 10.1016/j.ejphar.2020.173159. Epub 2020 Apr 29.

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Selective inhibition of mitochondrial respiratory complexes controls the transition of microglia into a neurotoxic phenotype in situ. Brain Behav Immun. 2020 Aug;88:802-814. doi: 10.1016/j.bbi.2020.05.052. Epub 2020 May 21.

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Mild metabolic stress is sufficient to disturb the formation of pyramidal cell ensembles during gamma oscillations. J Cereb Blood Flow Metab. 2019 Dec 16:271678X19892657. doi: 10.1177/0271678X19892657. [Epub ahead of print


Institute of
Physiology and Pathophysiology

Heidelberg University

Im Neuenheimer Feld 326

69120 Heidelberg

Germany

Phone:+49 6221 54-4056
Fax:+49 6221 54-6364
E-mail:susanne.bechtel@
physiologie.uni-heidelberg.de