AG Witting - Neuroinflammation

Inflammation in the form of activated microglial cells and a change in the metabolic system are early hallmark of neurodegenerative diseases. Microglial cells are the immune cells of the brain and survey their environment to detect insults. Activated by insults they can either be beneficial by releasing growth factors and remove debris or be harmful by releasing neurotoxic substances. The positive effects of anti-inflammatory treatments suggest an active detrimental role of microglial cells in neurodegenerative diseases.

Our Group focuses on the mechanism by which mitochondrial dysfunction in microglial cells influences neurodegenerative disease progression with the specific hypothesis that mitochondrial dysfunction associated with neurodegenerative diseases activate microglial cells with detrimental consequences for neurons and that targeted drug therapy would likely inhibit or even halt the destructive degenerations related to these diseases.

Quantification of endocannabinoids by gas chromatography/ mass spectrometry (GC/MS). Investigating phagocytosis and migration of microglia on human brain slices. Quantification of enzyme kinetics by biochemical methods using radioactive labeled substrates. Induction and monitoring of EAE in mice. Treatment of ALS mice with cannabinoids by subcutaneous mini pumps. Primary cultures of neurons, microglia, astroglia and oligodendrocytes. Small interfering RNA. Perfusion fixation; tissue collection; cryostat sectioning; histology: immunohistochemistry. ELISA. FACS-Analysis. Microchemotaxis Assays. Western Blot. Video-microscopy. Calcium-imaging.

Anke Witting, PhD: anke.witting[at]uni-ulm.de

• Witting A., Chen L., Cudaback E., Straiker A., Walter L., Rickman B., Möller T., Brosnan C. and Stella N. (2006) Experimental autoimmune encephalomyelitis disrupts endocannabinoid-mediated neuroprotection. PNAS 103 (16): 6362-7
• Eljaschewitsch E., Witting A., Mawrin C., Lee T., Schmidt P.M., Wolf S., Hoertnagl H., Raine C.S., Schneider-Stock R., Nitsch R. and Ullrich O. (2006) The endocannabinoid anandamide protects neurons during CNS inflammation by induction of MKP-1 in microglial cells. NEURON 49 (1): 67-79
• Weydt P., Hong S.Y., Witting A., Moeller T., Stella N. and Kliot M. (2005) Cannabinol delays symptom onset in SOD1 (G93A) transgenic mice without affecting survival. AMYOTROPH LATERAL SCLER OTHER MOTOR NEURON DISORD 6 (3): 182-184
• Witting A., Weydt P., Hong S.Y., Kliot M., Möller T. and Stella N. (2004) Endocannabinoids accumulate in spinal cord of SOD1 G93A transgenic mice. J NEUROCHEM 89 (6): 1555-1557
• Witting A., Walter L., Wacker J., Möller T. and Stella N. (2004) P2X7 receptors control 2-arachidonylglycerol production by microglial cells. PNAS 101 (9): 3214-3219
• Witting A. and Stella N. (2004) Cannabinoid signaling in glial cells in health and disease. CURR NEUROPHARM 2:115-124
• Walter L., Franklin A., Witting A., Wade C., Xie Y., Kunos G., Mackie K., and Stella N. (2003) Nonpsychotropic cannabinoid receptors regulate microglial cell migration. J NEUROSCI 23 (4): 1398-1405
• Walter L., Franklin A., Witting A., Möller T., and Stella N. (2002) Astrocytes in culture produce anandamide and other acylethanolamides. J BIOL CHEM 277 (23): 20869-20876
• Witting A., Müller P., Herrmann A., Kettenmann H., and Nolte C. (2000) Phagocytic clearance of apoptotic neurons by microglia/brain macrophages in vitro: Involvement of lectin-, integrin-, and phosphatidylserine-mediated recognition. J NEUROCHEM 75 (3): 1060-1070