Medicine and Health Sciences Commons^™

Optimal Bone Strength And Mineralization Requires The Type 2 Iodothyronine Deiodinase In Osteoblasts, J. H. D. Bassett, Alan Boyde, Peter G. T. Howell, Richard H. Bassett, Thomas M. Galliford, Marta Archanco, Holly Evans, Michelle A. Lawson, Peter Croucher, Donald L. St. Germain, Valerie A. Galton, Graham R. Williams

Dartmouth Scholarship

Hypothyroidism and thyrotoxicosis are each associated with an increased risk of fracture. Although thyroxine (T4) is the predominant circulating thyroid hormone, target cell responses are determined by local intracellular availability of the active hormone 3,5,3'-L-triiodothyronine (T3), which is generated from T4 by the type 2 deiodinase enzyme (D2). To investigate the role of locally produced T3 in bone, we characterized mice deficient in D2 (D2KO) in which the serum T3 level is normal. Bones from adult D2KO mice have reduced toughness and are brittle, displaying an increased susceptibility to fracture. This phenotype is characterized by a 50% reduction in bone …

Neuropilin 1 Directly Interacts With Fer Kinase To Mediate Semaphorin3a-Induced Death Of Cortical Neurons, Susan X. Jiang, Shawn N. Whitehead, Amy Aylsworth, Bogdan Zurakowski, Kenneth Chan, Jianjun Li, Sheng T. Hou

Anatomy and Cell Biology Publications

Neuropilins (NRPs) are receptors for the major chemorepulsive axonal guidance cue semaphorins (Sema). The interaction of Sema3A/NRP1 during development leads to the collapse of growth cones. Here we show that Sema3A also induces death of cultured cortical neurons through NRP1. A specific NRP1 inhibitory peptide ameliorated Sema3A-evoked cortical axonal retraction and neuronal death. Moreover, Sema3A was also involved in cerebral ischemia-induced neuronal death. Expression levels of Sema3A and NRP1, but not NRP2, were significantly increased early during brain reperfusion following transient focal cerebral ischemia. NRP1 inhibitory peptide delivered to the ischemic brain was potently neuroprotective and prevented the loss of …

Dopamine Neuron Stimulating Actions Of A Gdnf Propeptide, Luke H. Bradley, Josh Fuqua, April Richardson, Jadwiga Turchan-Cholewo, Yi Ai, Kristen A. Kelps, John D. Glass, Xiuquan He, Zhiming Zhang, Richard Grondin, O. Meagan Littrell, Peter Huettl, Francois Pomerleau, Don M. Gash, Greg A. Gerhardt

Neuroscience Faculty Publications

BACKGROUND: Neurotrophic factors, such as glial cell line-derived neurotrophic factor (GDNF), have shown great promise for protection and restoration of damaged or dying dopamine neurons in animal models and in some Parkinson's disease (PD) clinical trials. However, the delivery of neurotrophic factors to the brain is difficult due to their large size and poor bio-distribution. In addition, developing more efficacious trophic factors is hampered by the difficulty of synthesis and structural modification. Small molecules with neurotrophic actions that are easy to synthesize and modify to improve bioavailability are needed.

METHODS AND FINDINGS: Here we present the neurobiological actions of dopamine …

Progressive Changes In Microglia And Macrophages In Spinal Cord And Peripheral Nerve In The Transgenic Rat Model Of Amyotrophic Lateral Sclerosis, David J. Graber, William F. Hickey, Brent T. Harris

Dartmouth Scholarship

The role of neuroinflammation in motor neuron death of amyotrophic lateral sclerosis (ALS) is unclear. The human mutant superoxide dismutase-1 (hmSOD1)-expressing murine transgenic model of ALS has provided some insight into changes in microglia activity during disease progression. The purpose of this study was to gain further knowledge by characterizing the immunological changes during disease progression in the spinal cord and peripheral nerve using the more recently developed hmSOD1 rat transgenic model of ALS. Using immunohistochemistry, the extent and intensity of tissue CD11b expression in spinal cord, lumbar nerve roots, and sciatic nerve were evaluated in hmSOD1 rats that were …