Prof. Dr. Jan Siemens

Institute of Pharmacology, Medical Faculty Heidelberg, Heidelberg University

Prof. Dr. Hilmar Bading

Institute of Neurobiology, Heidelberg University

 

Activity-regulated gene programs leading to short-term and long-term metabolic plasticity in the spinal cord: role in acute and pathological forms of pain
 

The dorsal spinal cord is the first relay station for incoming noxious signals that arise from primary somatosensory afferent neurons. Aberrant gene regulation is a major contributor driving the transition from acute to chronic pain states. How pain-induced transcriptional changes shape functional alterations of diverse spinal cell types is only starting to be understood. We have identified a metabolic signalling molecule that is highly up-regulated in astrocytes upon painful stimulation. Preliminary metabolite analysis suggests that major energy-metabolic alterations occur in both spinal glia and neurons in the context of on-going and extended painful stimulation. These findings not only raise the question as to what signals trigger these metabolic alterations but, more generally, how spinal energy metabolism affects pain sensation. We aim to understand how pain-related synaptic activity induces metabolic state changes in neuroglial networks. Based on the uncovered metabolic signaling pathways, we aim to manipulate energy metabolism in the spinal cord in the context of pathological forms of pain in order to understand how metabolite flux affects pain responses in animal models.

Project related Publications (not necessarily from my group):

Peer-reviewed publications: (past and present CRC PIs are marked in bold)

Yan, J., Bengtson, C.P., Buchthal, B., Hagenston, A.M., Bading, H. (2020). Coupling of NMDA receptors and TRPM4 guides discovery of unconventional neuroprotectants. Science 370: eaay3302.

Mauceri D, Buchthal B, Hemstedt TJ, Weiss U, Klein CD, Bading H. Nasally delivered VEGFD mimetics mitigate strokeinduced dendrite loss and brain damage. Proc Natl Acad Sci USA. 2020 Apr 14;117(15):8616-8623. doi: 10.1073/pnas.2001563117. Epub 2020 Mar 30.

Bas-Orth C, Tan YW, Lau D, Bading H. Synaptic Activity Drives a Genomic Program That Promotes a Neuronal Warburg Effect. J Biol Chem 2017;292(13):5183-5194.

Chandrasekar A, Olde Heuvel F, Tar L, Hagenston AM, Palmer A, Linkus B, Ludolph AC, Huber-Lang M, Boeckers T, Bading H, Roselli F. Parvalbumin Interneurons Shape Neuronal Vulnerability in Blunt TBI. Cereb Cortex 2018. Hagenston AM, Simonetti M. Neuronal calcium signaling in chronic pain. Cell Tissue Res 2014;357(2):407-426.

Hanack C, Moroni M, Lima WC, Wende H, Kirchner M, Adelfinger L, Schrenk-Siemens K, Tappe-Theodor A, Wetzel C, Kuich PH, Gassmann M, Roggenkamp D, Bettler B, Lewin GR, Selbach M, Siemens J. GABA blocks pathological but not acute TRPV1 pain signals. Cell 2015;160(4):759-770.

Litke C, Bading H,

Mauceri D. Histone deacetylase 4 shapes neuronal morphology via a mechanism involving regulation of expression of vascular endothelial growth factor D. J Biol Chem 2018;293(21):8196-8207. Mauceri D, Hagenston AM, Schramm K, Weiss U, Bading H. Nuclear Calcium Buffering Capacity Shapes Neuronal Ar-chitecture. J Biol Chem 2015;290(38):23039-23049.

Rostock C, Schrenk-Siemens K, Pohle J, Siemens J. Human vs. Mouse Nociceptors - Similarities and Differences. Neu-roscience 2018;387:13-27.

Schrenk-Siemens K, Wende H, Prato V, Song K, Rostock C, Loewer A, Utikal J, Lewin GR, Lechner SG, Siemens J. PIEZO2 is required for

Simonetti M, Hagenston AM, Vardeh D, Freitag HE, Mauceri D, Lu J, Satagopam VP, Schneider R, Costigan M, Bading H, Kuner R. Nuclear calcium signaling in spinal neurons drives a genomic program required for persistent inflam-matory pain. Neuron 2013;77(1):43-57.

Song K, Wang H, Kamm GB, Pohle J, Reis FC, Heppenstall P, Wende H, Siemens J. The TRPM2 channel is a hypotha-lamic heat sensor that limits fever and can drive hypothermia. Science 2016;353(6306):1393-1398.

People:

Anna Hagenston-Hertle (Hertle(at)nbio.uni-heidelberg.de)

Sebastian Marty (sebastian.marty(at)pharma.uni-heidelberg.de)

News

  • ECNP Neuropsychopharmacology Award

    Congratulations to Prof. Dr. Valery Grinevich (Project B02)!

     

    Read more ...  
  • Silvia King Award 2021

    Congratulations to Dr. Johann Jende (Project A03)!

     

    Read more ...  
  • SFB1158 and NIKON BioImage Analysis Workshop

    Registration deadline extended until 30 April 2021

     

    Read more ...  
  • Latest research from Project B02

    (New paper published in Nature Neuroscience)

     

    Read more ...  
  • Webinar, "Multiomics Single Cell Analysis and Spatial Gene Expression Analysis of Intact Tissues"

    Register now for this webinar on February 17, 2021

     

    Read more ...