To systematically understand the molecular events that underlie biological phenomena, we must develop methods to integrate enormous amount of genomic and proteomic data. The integration of molecular data should go beyond the construction of biochemical cascades among molecules to include tying the biochemical phenomena to physical events. For the behavior and guidance of growth cones, it remains largely unclear how biochemical events in the cytoplasm are linked to the morphological changes of the growth cone. The network of Rho family small GTPases is thought to be a computational system that translates external signals into the regulation of growth cone movement and axon guidance. We take a computational approach to simulate the biochemical signaling cascade involving members of the Rho family of GTPases and examine their potential roles in growth-cone motility and axon guidance. We first examine the qualitative characteristics of the GTPase crosstalk. We show that the GTPase activities can exhibit switch...

Electrical stimulation of the proximal stump of a cut peripheral nerve at the time of its surgical repair results in an enhancement of the regeneration of its axons. Stimulation also results in an increase in the mRNA for brain derived neurotrophic factor and its receptor, trkB, in motoneurons and dorsal root ganglion cells. The regeneration of axons through nerve grafts was used to evaluate whether the growth promoting effect of electrical stimulation is due to an enhancement of cell autonomous neurotrophin signaling in the regenerating axons or enhancement of signaling from neurotrophins in the environment surrounding them. Experiments were conducted using the thy-1-YFP-H mouse, in which a subset of peripheral axons is marked by the presence of yellow fluorescent protein (YFP). A single one hour application of electrical stimulation at the time of surgical repair of the cut common fibular (CF) nerve results in a doubling of the median length of profiles of regenerating YFP+ axons through nerve grafts fro...

We tested the hypothesis that netrin is as an inhibitor to axon growth in adult white matter. An in vitro assay was established to neutralize potential netrin-mediated inhibition of axon outgrowth via Unc5 receptor signaling. Embryonic day 15 (E15) rat spinal cords were isolated, motor columns were dissected and Unc5H1- and Unc5H3- expressing motor neurons were enzymatically dissociated and plated on coverslips that were coated with myelin prepared from adult rat spinal cord. Unc5H2 receptor bodies, fusion proteins between the extracellular domain of the netrin receptor Unc5H2 and human Fc IgG, were engineered to neutralize netrin-1. Axon outgrowth from E15 spinal motor neurons increased by 82% (p < 0.001) after treatment of myelin with soluble Unc5H2 receptor bodies, from a mean neurite length of 49 µm +/- 0.6 µm (SEM) using control Fc to 89 µm +/- 1.3 µm (SEM) using the receptor body. Effects were observed in a dose dependent manner. These results suggest that physiological levels of netrin-1 contained w...

To investigate the immune response to sciatic nerve injury (SNI), adult C57BL/6 mice were subjected to a mid-thigh crush injury. To assess the presence, abundance and phenotypes of immune cells that respond to SNI, we used immunofluorescence staining of...

Bidirectional protein trafficking is essential for neurons to exchange information regarding the health of their cell soma and distal axons and thus coordinate survival versus degeneration decisions for these two subcellular locations. Healthy neurons t...

Biomaterials in combination with other experimental approaches such as cell grafts have shown some promise in promoting tissue sparing, increasing remyelination and enhancing axonal regeneration in the injured spinal cord by providing physical and chemi...

In axons, mitochondria are transported via microtubules and motor proteins. On the other hand, stationary mitochondria stopping movement are also widely distributed and are considered to be involved in axon branching and elongation. The systems regulati...

Brain connectivity and function depend on the precise formation of neuronal connections during development. In the central nervous system, most axonal projections are organized into topographic maps according to the spatial organization of the neurons t...

Cortical neuron network activity is altered during periods of arousal, locomotion, exploration, and attention. These brain states are also accompanied by physiological changes such as pupil dilation and motor movements, including running. The mouse neoc...

Cerebral ischemia causes severe cell death or injury including axon breakdown or retraction in the brain. Axonregeneration is crucial for the functional recovery of injured neurons or brains after ischemia/reperfusion (I/R); however, this process has be...