We employ various histological and biochemical techniques to localize and visualize and to interfere with this highly reactive and rather elusive molecule and its signaling pathways. Our standard model organism is the locust (Locusta migratoria) which is very useful because of its large size and robustness, but we also work with Drosophila, mosquitos, other invertebrates, and vertebrate cell lines. We could show that in the locust CNS, NO is produced in response to nerve injury and that it facilitates nerve regeneration.

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NO-producing cells in the insect CNS, Cells responding to NO producing cGMP, Regenerating nerve fibers in locust brain

Literature

Stern M, Bicker G (2008) Nitric oxide regulates axonal regeneration in an insect embryonic CNS. Dev. Neurobiol. 68:295-308.

Stern M, Böger N, Eickhoff R, Kerßen U, Lorbeer C, Ziegler M, Martinelli GP, Holstein GR, Bicker G (2010) Development of nitrergic neurons in the nervous system of the locust embryo. J. Comp. Neurol. 518:1157–1175.

Scheiblich H, Roloff F, Singh V, Stangel M, Stern M, Bicker G (2014) Nitric oxide / cyclic GMP signaling regulates motility of a microglial cell line in vitro. Brain Res. 1564:9-21.

A further field of our research interests is developmental neurotoxicity (DNT). Exposure to pesticides or other toxins during in utero and early postnatal development can cause a wide range of neurological defects. In vivo testing of chemicals in vertebrates is cost-intensive. In collaboration with the virtual center for replacement of animal experiments, we are involved in the development of alternative methods to test the neurotoxic potential of chemicals. We employ a human neuronal precursor cell line (Ntera2) to develop standardized tests for toxin effects on fundamental processes of brain development like cell migration, neuronal differentiation, and neurite outgrowth. More advanced developmental processes, like axonal growth cone navigation along multiple morphogen gradients can hardly be addressed in simple cell culture systems. Making use of our expertise on the insect nervous system, we have recently developed a test method for DNT on axon navigation using embryonic locust limb bud pioneer neurons as a test system.

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DNT assay on developing human neuronan cell line, DNT assay on locust limb bud pioneer neurons

Literature

Stern M, Gierse A, Tan S, Bicker G (2014) Human Ntera-2 cells as a predictive in vitro test system for developmental neurotoxicity. Arch. Toxicol. 88:127–136.

Bergmann GA, Frömbling S, Joseph N, Bode K, Bicker G, Stern M (2019) An intact insect embryo for developmental neurotoxicity testing of directed axonal elongation. ALTEX 36(4):643-649. doi:10.14573/altex.1901292

Bode K, Bohn M, Reitmeier J, Betker P, Stern M, Bicker G (2020) A locust embryo as predictive developmental neurotoxicity testing system for pioneer axon pathway formation. Arch Toxicol. 94: 4099-4113. doi: 10.1007/s00204-020-02929-6.

Schmitz A, Dempewolf S, Tan S, Bicker G, Stern M (2021) Developmental neurotoxicity of fipronil and rotenone on a human neuronal in vitro test system. Neurotox. Res. doi.org/10.1007/s12640-021-00364-8