Impact of Neurotrophins on gap junctions in regard to protection against ischemia

• Applicant: Dr. Regina Hanstein
• Subject Area: Molecular Biology and Physiology of Neurons and Glial Cells
• Term: from 2009 to 2012
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 119418094

Gap junctions are important for the homeostasis of the CNS and in the periphery under physiological conditions as they connect the cytoplasms of adjacent cells, thus coordinating cell-cell communication. Connexin43 (Cx43) is expressed throughout human tissues; it is the major expressed Cx-isoform in brain and heart. Mutation or altered expression of Cx43 has been observed in many pathological disorders, like ischemia. In ischemia, a main feature of neurological disability and heart diseases, the amount, distribution and functions of gap junctions are radically altered, leading to a decrease in cell-cell communication. Gap junctional uncoupling might prevent transfer of toxic molecules between cells, and thus contribute to cell protection. On the other hand, it might have toxic effects, e.g. in the brain, where it disturbs the support of neurons via the astrocyte syncytium, and in the heart, where it causes arrhythmias and contractile dysfunction. Gap junction expression and function are regulated by growth factors and hormones. An impact of neurotrophins, like BDNF and NGF, on connexins has just recently been discovered, demonstrating an upregulation of Cx43 expression and gap junctional coupling. Neurotrophins are expressed in the brain and periphery, where they promote survival of neurons as well as of non-neuronal cells. Therefore, the relevance of gap junctioncommunication for neurotrophin-induced protection against ischemic insults in the brain and heart will be analyzed, as there is a crucial need for the development of protective therapies in ischemia.

• DFG Programme: Research Fellowships
• International Connection: USA
• Host: Professor David Spray, Ph.D.