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Huntington's disease (HD) is a neurodegenerative disorder caused by a tandem repeat expansion encoding a polyglutamine tract in the huntingtin protein. HD involves progressive psychiatric, cognitive, and motor symptoms, the selective pathogenesis of which remains to be mechanistically elucidated. There are a range of different brain regions, including the(More)
Adult hippocampal neurogenesis (AHN) is modulated by a variety of factors through effects on the proliferation-differentiation-survival regulatory axis. We have employed growth hormone receptor knockout (GH-R-/-) and suppressor of cytokine signaling-2 transgenic (SOCS-2 Tg) mice as models of altered GH-signaling to assess their affects on basal and(More)
Schizophrenia is a devastating psychiatric illness with a complex pathophysiology. We have recently documented schizophrenia-like endophenotypes in phospholipase C-β1 knockout (PLC-β1(-/-)) mice, including deficits in prepulse inhibition, hyperlocomotion, and cognitive impairments. PLC-β1 signals via multiple G-protein coupled receptor pathways implicated(More)
Erythropoietin is a primary regulator of erythropoiesis in the hematopoietic system. More recently erythropoietin has been shown to play a role in neurogenesis and provide neurotrophic support to injured CNS tissue. Here the effects of large systemic doses of erythropoietin on basal levels of adult hippocampal neurogenesis in mice were examined. A 7-day(More)
Neuronal differentiation of neural progenitor cells is regulated by a variety of growth and transcription factors, that not only regulate cell fate of the progenitor cells but that can also regulate neuronal morphology. Suppressor of cytokine signaling-2 (SOCS2) is an intracellular regulator of Growth Hormone (GH) signaling that is expressed in neural stem(More)
Developing an understanding of factors that regulate development of the nervous system is important if we hope to be able to repair the nervous system after injury or disease. Suppressor of cytokine signaling-2 (SOCS2) is an intracellular regulator of cytokine signaling that blocks the inhibitory effects of growth hormone on neuronal differentiation and(More)
Erythropoietin (EPO) enhances neurogenesis, neuroprotection and regeneration. Here, we examined the effects of EPO on axonal and dendritic growth in a model of neuronal polarization. EPO did not effect survival or the polarized morphology of hippocampal neurons but its effect on neurite outgrowth depended upon the stage of polarization. When added to(More)
Recently we have shown that growth hormone (GH) inhibits neuronal differentiation and that this process is blocked by suppressor of cytokine signalling-2 (SOCS2). Here we examine several cortical and subcortical neuronal populations in GH hyper-responsive SOCS2 null (-/-) mice and GH non-responsive GH receptor null (GHR-/-) mice. While SOCS2-/- mice showed(More)
Huntington's disease (HD) is a fatal neurodegenerative disorder affecting a range of cellular and molecular functions in the brain. Deficits in adult hippocampal neurogenesis (AHN) have been documented in the R6/1 mouse model of HD. Here we examined basal and running-induced neuronal precursor proliferation in adult female and male R6/1 HD mice. We further(More)
Despite the well established central pathophysiology of Huntington's disease (HD), less is known about systemic impairments that are emerging as significant contributors to the morbidity of this neurodegenerative condition. Given the evidence of neuroendocrine dysfunction in HD patients and the pro-neural properties of sex-hormones, we explored the(More)