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.