Neuronal regeneration of induced by exposure to hypergravity

Abstract

Neuronal activity is the key modulator of nearly every aspect of behavior. Cognition, learning and memory as well as motion tasks are based on by neuronal transmission. Alterations or even disruptions of the transmission of synaptic signals are the main cause of many neurological disorders. A fundamental concern in the treatment of most neuropathologies is the re-integration of synaptic inputs to previously impaired neuronal networks that were affected e.g. by spinal cord injury, head trauma or other types of lesions to the nervous system. The regeneration of injured neuronal fibers is nearly completely inhibited by the scar tissue that forms upon damage to the surrounding tissue. Therefore regeneration of axonal projections through the lesion site is nearly impossible resulting in sustained damage of the tissue. To better understand the regeneration of nervous tissue, primary murine hippocampal neurons are used as a model closely related to human neural tissue. The influential role of increased gravity on neuronal development will be investigated by analyses of the different developmental stages, including neuritogenesis, neuronal polarization and further in maturation processes like synaptogenesis or synaptic integration in neural networks. Each of these developmental steps could play a role at a certain level in neuronal regeneration in vivo. Exposure of primary neurons to hypergravity conditions (2g) induced an increased number of neurites (about 30%) and longer projections (about 20%) compared to the control at 1g. At later stages of development mature synaptic contacts were formed under hypergravity conditions. In addition, the formation of glial scar tissues could be inhibited by exposure to hypergravity as well. Primary cultured astrocytes, the major cell type involved in glial scar formations, showed decreased lamellipodial protrusions and a deficit in cell spreading due to exposure to hypergravity conditions. Our results indicate hypergravity as an innovative measure to artificially stabilize cytoskeletal components of neuronal cells, enabling them to counteract the restricted process of neurite outgrowth and therefore enhance axon regeneration in previously traumatized networks.