Frank Kirchhoff

Molecular Physiology

 

Our research focuses on the molecular and cellular mechanisms of neuron-glia interaction in the central nervous system.

 

We are pursuing two main research questions:

 

  1. How do glial transmitter receptors sense and modulate synaptic transmission? What is the impact for living organisms?

  2. How do glial cells respond to acute injuries within the central nervous system?

For functional analysis we generated (and are still continuing to develop) transgenic mouse models with cell-type specific expression of various fluorescent proteins (FPs) and inducible gene deletion. We are applying a combination of biochemical and molecular biological methods together with imaging techniques such as two-photon laser-scanning microscopy (2P-LSM) or CCD imaging.

 

 

 

Projects

Transgenic mice with cell-type specific fluorescent

Well-known is our mouse line in which astrocytes of various brain regions express the green fluorescent protein EGFP under the control of the human astroglia-specific glial fibrillary acidic protein (GFAP) promoter TgN(GFAP-EGFP). During the last years we expanded the transgenic astroglia labelling using the blue (ECFP) and red (mRFP) fluorescent proteins. These transgenic lines were complemented with lines in which EYFP or HcRed are driven by the mouse Thy-1 mini-gene in neurones. Expression of DsRed in oligodendrocytes was achieved using a mouse proteolipid protein (PLP) mini-gene. Currently, we are evaluating photoswitchable fluorescent proteins or ion channels for their use in transgenic mice.

 

Role of astroglial transmitter receptors for brain function

Recently, we generated the transgenic mouse line TgN(GFAP-CreERT2) in which the tamoxifen-sensitive Cre recombinase CreERT2 is expressed in astrocytes to take advantage of the Cre/loxP system. Currently, we are studying crosses of TgN(GFAP-CreERT2) mice with such in which transmitter receptor genes are flanked by loxP sites. We are currently analyzing whether induced astroglial receptor deletion results in ultrastructural changes, modulation of neurotransmission and behavioural abnormalities.

 

Glial responses during acute injuries of the central nervous system

An intrinsic property of all glial cell types (astrocytes, oligodendrocytes and microglia) is their strong activation during brain damage. We take advantage of our transgenic mouse lines and use them as reporters in brain pathology by applying in vivo 2P-LSM. Currently, we are focussing at acute lesions within the spinal cord. In particular, we ask: What are the distinct contributions of glial cells and their progenitors in brain damage? Is glia activation by acute CNS trauma accompanied by progenitor/stem cell activation? What is the fate of activated glia after scar formation and healing? Are there differences of glial responses in lesions during different phases of neuroinflammation?

 

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